73 results on '"Law CY"'
Search Results
2. The JCMT BISTRO Survey: A Spiral Magnetic Field in a Hub-filament Structure, Monoceros R2
- Author
-
Hwang, J, Kim, J, Pattle, K, Lee, CW, Koch, PM, Johnstone, D, Tomisaka, K, Whitworth, A, Furuya, RS, Kang, JH, Lyo, AR, Chung, EJ, Arzoumanian, D, Park, G, Kwon, W, Kim, S, Tamura, M, Kwon, J, Soam, A, Han, I, Hoang, T, Kim, KH, Onaka, T, Eswaraiah, C, Ward-Thompson, D, Liu, HL, Tang, X, Chen, WP, Matsumura, M, Hoang, TD, Chen, Z, Le Gouellec, VJM, Kirchschlager, F, Poidevin, F, Bastien, P, Qiu, K, Hasegawa, T, Lai, SP, Byun, DY, Cho, J, Choi, M, Choi, Y, Jeong, IG, Kang, M, Kim, H, Kim, KT, Lee, JE, Lee, SS, Lee, YH, Lee, H, Kim, MR, Yoo, H, Yun, HS, Chen, M, Di Francesco, J, Fiege, J, Fissel, LM, Franzmann, E, Houde, M, Lacaille, K, Matthews, B, Sadavoy, S, Moriarty-Schieven, G, Tahani, M, Ching, TC, Dai, YS, Duan, Y, Gu, Q, Law, CY, Li, D, Li, G, Li, HB, Liu, T, Lu, X, Qian, L, Wang, H, Wu, J, Xie, J, Yuan, J, Zhang, CP, Zhang, G, Zhang, Y, Zhou, J, Zhu, L, Berry, D, Friberg, P, Graves, S, Liu, J, Mairs, S, Parsons, H, Rawlings, M, Doi, Y, Hayashi, S, Hull, CLH, Inoue, T, Inutsuka, SI, Iwasaki, K, Kataoka, A, Hwang, J [0000-0001-7866-2686], Kim, J [0000-0002-1229-0426], Pattle, K [0000-0002-8557-3582], Lee, CW [0000-0002-3179-6334], Koch, PM [0000-0003-2777-5861], Johnstone, D [0000-0002-6773-459X], Tomisaka, K [0000-0003-2726-0892], Whitworth, A [0000-0002-1178-5486], Furuya, RS [0000-0003-0646-8782], Kang, JH [0000-0001-7379-6263], Lyo, AR [0000-0002-9907-8427], Chung, EJ [0000-0003-0014-1527], Arzoumanian, D [0000-0002-1959-7201], Park, G [0000-0001-8467-3736], Kwon, W [0000-0003-4022-4132], Kim, S [0000-0001-9333-5608], Tamura, M [0000-0002-6510-0681], Kwon, J [0000-0003-2815-7774], Soam, A [0000-0002-6386-2906], Han, I [0000-0002-9143-1433], Hoang, T [0000-0003-2017-0982], Kim, KH [0000-0001-9597-7196], Onaka, T [0000-0002-8234-6747], Eswaraiah, C [0000-0003-4761-6139], Ward-Thompson, D [0000-0003-1140-2761], Liu, HL [0000-0003-3343-9645], Tang, X [0000-0002-4154-4309], Chen, WP [0000-0003-0262-272X], Matsumura, M [0000-0002-6906-0103], Hoang, TD [0000-0002-3437-5228], Chen, Z [0000-0003-0849-0692], Le Gouellec, VJM [0000-0002-5714-799X], Kirchschlager, F [0000-0002-3036-0184], Poidevin, F [0000-0002-5391-5568], Bastien, P [0000-0002-0794-3859], Qiu, K [0000-0002-5093-5088], Hasegawa, T [0000-0003-1853-0184], Lai, SP [0000-0001-5522-486X], Byun, DY [0000-0003-1157-4109], Cho, J [0000-0003-1725-4376], Jeong, IG [0000-0002-5492-6832], Kang, M [0000-0002-5016-050X], Kim, KT [0000-0003-2412-7092], Lee, JE [0000-0003-3119-2087], Lee, SS [0000-0002-6269-594X], Lee, YH [0000-0001-6047-701X], Lee, H [0000-0003-3465-3213], Kim, MR [0000-0002-1408-7747], Yoo, H [0000-0002-8578-1728], Yun, HS [0000-0001-6842-1555], Di Francesco, J [0000-0002-9289-2450], Fissel, LM [0000-0002-4666-609X], Franzmann, E [0000-0003-2142-0357], Houde, M [0000-0003-4420-8674], Lacaille, K [0000-0001-9870-5663], Matthews, B [0000-0003-3017-9577], Moriarty-Schieven, G [0000-0002-0393-7822], Tahani, M [0000-0001-8749-1436], Ching, TC [0000-0001-8516-2532], Dai, YS [0000-0002-7928-416X], Gu, Q [0000-0002-2826-1902], Li, HB [0000-0003-2641-9240], Liu, T [0000-0002-5286-2564], Lu, X [0000-0003-2619-9305], Qian, L [0000-0003-0597-0957], Wu, J [0000-0001-7276-3590], Xie, J [0000-0002-2738-146X], Zhang, CP [0000-0002-4428-3183], Zhang, Y [0000-0002-5102-2096], Zhou, J [0000-0003-0356-818X], Berry, D [0000-0001-6524-2447], Friberg, P [0000-0002-8010-8454], Graves, S [0000-0001-9361-5781], Liu, J [0000-0002-4774-2998], Mairs, S [0000-0002-6956-0730], Parsons, H [0000-0002-6327-3423], Rawlings, M [0000-0002-6529-202X], Doi, Y [0000-0001-8746-6548], Hayashi, S [0000-0001-5026-490X], Hull, CLH [0000-0002-8975-7573], Inoue, T [0000-0002-7935-8771], Inutsuka, SI [0000-0003-4366-6518], Kataoka, A [0000-0003-4562-4119], and Apollo - University of Cambridge Repository
- Subjects
5101 Astronomical Sciences ,51 Physical Sciences - Abstract
We present and analyze observations of polarized dust emission at 850 μm toward the central 1 × 1 pc hub-filament structure of Monoceros R2 (Mon R2). The data are obtained with SCUBA-2/POL-2 on the James Clerk Maxwell Telescope (JCMT) as part of the B-fields in Star-forming Region Observations survey. The orientations of the magnetic field follow the spiral structure of Mon R2, which are well described by an axisymmetric magnetic field model. We estimate the turbulent component of the magnetic field using the angle difference between our observations and the best-fit model of the underlying large-scale mean magnetic field. This estimate is used to calculate the magnetic field strength using the Davis–Chandrasekhar–Fermi method, for which we also obtain the distribution of volume density and velocity dispersion using a column density map derived from Herschel data and the C18O (J = 3 − 2) data taken with HARP on the JCMT, respectively. We make maps of magnetic field strengths and mass-to-flux ratios, finding that magnetic field strengths vary from 0.02 to 3.64 mG with a mean value of 1.0 ± 0.06 mG, and the mean critical mass-to-flux ratio is 0.47 ± 0.02. Additionally, the mean Alfvén Mach number is 0.35 ± 0.01. This suggests that, in Mon R2, the magnetic fields provide resistance against large-scale gravitational collapse, and the magnetic pressure exceeds the turbulent pressure. We also investigate the properties of each filament in Mon R2. Most of the filaments are aligned along the magnetic field direction and are magnetically subcritical.
- Published
- 2022
- Full Text
- View/download PDF
3. B-fields in Star-forming Region Observations (BISTRO): Magnetic Fields in the Filamentary Structures of Serpens Main
- Author
-
Kwon, W, Pattle, K, Sadavoy, S, Hull, CLH, Johnstone, D, Ward-Thompson, D, Francesco, JD, Koch, PM, Furuya, R, Doi, Y, Le Gouellec, VJM, Hwang, J, Lyo, AR, Soam, A, Tang, X, Hoang, T, Kirchschlager, F, Eswaraiah, C, Fanciullo, L, Kim, KH, Onaka, T, Könyves, V, Kang, JH, Lee, CW, Tamura, M, Bastien, P, Hasegawa, T, Lai, SP, Qiu, K, Berry, D, Arzoumanian, D, Bourke, TL, Byun, DY, Chen, WP, Chen, HRV, Chen, M, Chen, Z, Ching, TC, Cho, J, Choi, Y, Choi, M, Chrysostomou, A, Chung, EJ, Coudé, S, Dai, S, Diep, PN, Duan, Y, Duan, HY, Eden, D, Fiege, J, Fissel, LM, Franzmann, E, Friberg, P, Friesen, R, Fuller, G, Gledhill, T, Graves, S, Greaves, J, Griffin, M, Gu, Q, Han, I, Hatchell, J, Hayashi, S, Houde, M, Inoue, T, Inutsuka, SI, Iwasaki, K, Jeong, IG, Kang, M, Karoly, J, Kataoka, A, Kawabata, K, Kemper, F, Kim, KT, Kim, G, Kim, MR, Kim, S, Kim, J, Kirk, J, Kobayashi, MIN, Kusune, T, Kwon, J, Lacaille, K, Law, CY, Lee, CF, Lee, YH, Lee, H, Lee, JE, Lee, SS, Li, D, Li, HB, Lin, SJ, Liu, SY, Liu, HL, Liu, J, Liu, T, Lu, X, Mairs, S, Matsumura, M, Kwon, W [0000-0003-4022-4132], Pattle, K [0000-0002-8557-3582], Sadavoy, S [0000-0001-7474-6874], Hull, CLH [0000-0002-8975-7573], Johnstone, D [0000-0002-6773-459X], Ward-Thompson, D [0000-0003-1140-2761], Francesco, JD [0000-0002-9289-2450], Koch, PM [0000-0003-2777-5861], Furuya, R [0000-0003-0646-8782], Doi, Y [0000-0001-8746-6548], Le Gouellec, VJM [0000-0002-5714-799X], Hwang, J [0000-0001-7866-2686], Lyo, AR [0000-0002-9907-8427], Soam, A [0000-0002-6386-2906], Tang, X [0000-0002-4154-4309], Hoang, T [0000-0003-2017-0982], Kirchschlager, F [0000-0002-3036-0184], Fanciullo, L [0000-0001-9930-9240], Kim, KH [0000-0001-9597-7196], Onaka, T [0000-0002-8234-6747], Könyves, V [0000-0002-3746-1498], Kang, JH [0000-0001-7379-6263], Tamura, M [0000-0002-6510-0681], Bastien, P [0000-0002-0794-3859], Lai, SP [0000-0001-5522-486X], Qiu, K [0000-0002-5093-5088], Arzoumanian, D [0000-0002-1959-7201], Bourke, TL [0000-0001-7491-0048], Byun, DY [0000-0003-1157-4109], Chen, WP [0000-0002-5519-0628], Chen, HRV [0000-0002-9774-1846], Chen, Z [0000-0003-0849-0692], Ching, TC [0000-0001-8516-2532], Cho, J [0000-0003-1725-4376], Chrysostomou, A [0000-0002-9583-8644], Chung, EJ [0000-0003-0014-1527], Coudé, S [0000-0002-0859-0805], Duan, HY [0000-0002-7022-4742], Eden, D [0000-0002-5881-3229], Fissel, LM [0000-0002-4666-609X], Franzmann, E [0000-0003-2142-0357], Friberg, P [0000-0002-8010-8454], Friesen, R [0000-0001-7594-8128], Fuller, G [0000-0001-8509-1818], Gledhill, T [0000-0002-2859-4600], Graves, S [0000-0001-9361-5781], Greaves, J [0000-0002-3133-413X], Gu, Q [0000-0002-2826-1902], Hatchell, J [0000-0002-4870-2760], Houde, M [0000-0003-4420-8674], Inoue, T [0000-0002-7935-8771], Inutsuka, SI [0000-0003-4366-6518], Iwasaki, K [0000-0002-2707-7548], Kang, M [0000-0002-5016-050X], Kataoka, A [0000-0003-4562-4119], Kawabata, K [0000-0001-6099-9539], Kemper, F [0000-0003-2743-8240], Kim, KT [0000-0003-2412-7092], Kim, G [0000-0003-2011-8172], Kim, MR [0000-0002-1408-7747], Kim, S [0000-0001-9333-5608], Kim, J [0000-0002-1229-0426], Kirk, J [0000-0002-4552-7477], Kobayashi, MIN [0000-0003-3990-1204], Kusune, T [0000-0002-9218-9319], Kwon, J [0000-0003-2815-7774], Lacaille, K [0000-0001-9870-5663], Law, CY [0000-0003-1964-970X], Lee, CF [0000-0002-3024-5864], Lee, YH [0000-0001-6047-701X], Lee, H [0000-0003-3465-3213], Lee, JE [0000-0003-3119-2087], Lee, SS [0000-0002-6269-594X], Li, D [0000-0003-3010-7661], Li, HB [0000-0003-2641-9240], Lin, SJ [0000-0002-6868-4483], Liu, SY [0000-0003-4603-7119], Liu, J [0000-0002-4774-2998], Lu, X [0000-0003-2619-9305], Mairs, S [0000-0002-6956-0730], Matsumura, M [0000-0002-6906-0103], and Apollo - University of Cambridge Repository
- Subjects
5101 Astronomical Sciences ,Interstellar Matter and the Local Universe ,51 Physical Sciences ,Astrophysics::Galaxy Astrophysics - Abstract
We present 850 μm polarimetric observations toward the Serpens Main molecular cloud obtained using the POL-2 polarimeter on the James Clerk Maxwell Telescope as part of the B-fields In STar-forming Region Observations survey. These observations probe the magnetic field morphology of the Serpens Main molecular cloud on about 6000 au scales, which consists of cores and six filaments with different physical properties such as density and star formation activity. Using the histogram of relative orientation (HRO) technique, we find that magnetic fields are parallel to filaments in less-dense filamentary structures where N H 2 < 0.93 × 10 22 cm−2 (magnetic fields perpendicular to density gradients), while they are perpendicular to filaments (magnetic fields parallel to density gradients) in dense filamentary structures with star formation activity. Moreover, applying the HRO technique to denser core regions, we find that magnetic field orientations change to become perpendicular to density gradients again at N H 2 ≈ 4.6 × 10 22 cm−2. This can be interpreted as a signature of core formation. At N H 2 ≈ 16 × 10 22 cm−2, magnetic fields change back to being parallel to density gradients once again, which can be understood to be due to magnetic fields being dragged in by infalling material. In addition, we estimate the magnetic field strengths of the filaments (B POS = 60–300 μG)) using the Davis–Chandrasekhar–Fermi method and discuss whether the filaments are gravitationally unstable based on magnetic field and turbulence energy densities.
- Published
- 2022
- Full Text
- View/download PDF
4. The JCMT BISTRO survey: An 850/450μm polarization study of NGC 2071IR in Orion B
- Author
-
Lyo, AR, Kim, J, Sadavoy, S, Johnstone, D, Berry, D, Pattle, K, Kwon, W, Bastien, P, Onaka, T, Di Francesco, J, Kang, JH, Furuya, R, Hull, CLH, Tamura, M, Koch, PM, Ward-Thompson, D, Hasegawa, T, Hoang, T, Arzoumanian, D, Lee, CW, Lee, CF, Byun, DY, Kirchschlager, F, Doi, Y, Kim, KT, Hwang, J, Diep, PN, Fanciullo, L, Lee, SS, Park, G, Yoo, H, Chung, EJ, Whitworth, A, Mairs, S, Soam, A, Liu, T, Tang, X, Coudé, S, André, P, Bourke, TL, Chen, HRV, Chen, Z, Chen, WP, Chen, M, Ching, TC, Choi, M, Choi, Y, Chrysostomou, A, Dai, S, Zhang, CP, Duan, HY, Duan, Y, Cho, J, Eden, D, Eswaraiah, C, Eyres, S, Fiege, J, Fissel, LM, Franzmann, E, Friberg, P, Friesen, R, Fuller, G, Gledhill, T, Graves, S, Greaves, J, Griffin, M, Gu, Q, Han, I, Hatchell, J, Hayashi, S, Houde, M, Inoue, T, Inutsuka, SI, Iwasaki, K, Jeong, IG, Kang, M, Kataoka, A, Kawabata, K, Kim, G, Kim, MR, Kim, S, Kim, KH, Kirk, J, Kobayashi, MIN, Kemper, F, Könyves, V, Kusune, T, Kwon, J, Lacaille, K, Lai, SP, Lee, JE, Lee, YH, Lee, H, Li, D, Li, HB, Liu, HL, Law, CY, Liu, J, Liu, SY, Lyo, AR [0000-0002-9907-8427], Kim, J [0000-0002-1229-0426], Johnstone, D [0000-0002-6773-459X], Pattle, K [0000-0002-8557-3582], Kwon, W [0000-0003-4022-4132], Bastien, P [0000-0002-0794-3859], Onaka, T [0000-0002-8234-6747], Kang, JH [0000-0001-7379-6263], Furuya, R [0000-0003-0646-8782], Hull, CLH [0000-0002-8975-7573], Tamura, M [0000-0002-6510-0681], Koch, PM [0000-0003-2777-5861], Ward-Thompson, D [0000-0003-1140-2761], Hoang, T [0000-0003-2017-0982], Arzoumanian, D [0000-0002-1959-7201], Lee, CF [0000-0002-3024-5864], Byun, DY [0000-0003-1157-4109], Kirchschlager, F [0000-0002-3036-0184], Doi, Y [0000-0001-8746-6548], Kim, KT [0000-0003-2412-7092], Hwang, J [0000-0001-7866-2686], Lee, SS [0000-0002-6269-594X], Park, G [0000-0001-8467-3736], Yoo, H [0000-0002-8578-1728], Chung, EJ [0000-0003-0014-1527], Mairs, S [0000-0002-6956-0730], Soam, A [0000-0002-6386-2906], Liu, T [0000-0002-5286-2564], Tang, X [0000-0002-4154-4309], Coudé, S [0000-0002-0859-0805], André, P [0000-0002-3413-2293], Bourke, TL [0000-0001-7491-0048], Chen, Z [0000-0003-0849-0692], Chen, WP [0000-0002-5519-0628], Ching, TC [0000-0001-8516-2532], Chrysostomou, A [0000-0002-9583-8644], Zhang, CP [0000-0002-4428-3183], Cho, J [0000-0003-1725-4376], Eden, D [0000-0002-5881-3229], Franzmann, E [0000-0003-2142-0357], Friberg, P [0000-0002-8010-8454], Friesen, R [0000-0001-7594-8128], Fuller, G [0000-0001-8509-1818], Gledhill, T [0000-0002-2859-4600], Graves, S [0000-0001-9361-5781], Gu, Q [0000-0002-2826-1902], Hatchell, J [0000-0002-4870-2760], Houde, M [0000-0003-4420-8674], Inoue, T [0000-0002-7935-8771], Inutsuka, SI [0000-0003-4366-6518], Iwasaki, K [0000-0002-2707-7548], Kang, M [0000-0002-5016-050X], Kataoka, A [0000-0003-4562-4119], Kawabata, K [0000-0001-6099-9539], Kim, G [0000-0003-2011-8172], Kim, MR [0000-0002-1408-7747], Kim, S [0000-0001-9333-5608], Kirk, J [0000-0002-4552-7477], Kobayashi, MIN [0000-0003-3990-1204], Kemper, F [0000-0003-2743-8240], Könyves, V [0000-0002-3746-1498], Kusune, T [0000-0002-9218-9319], Kwon, J [0000-0003-2815-7774], Lacaille, K [0000-0001-9870-5663], Lai, SP [0000-0001-5522-486X], Lee, JE [0000-0003-3119-2087], Lee, YH [0000-0001-6047-701X], Lee, H [0000-0003-3465-3213], Li, D [0000-0003-3010-7661], Li, HB [0000-0003-2641-9240], Law, CY [0000-0003-1964-970X], Liu, J [0000-0002-4774-2998], Liu, SY [0000-0003-4603-7119], and Apollo - University of Cambridge Repository
- Subjects
5101 Astronomical Sciences ,51 Physical Sciences - Abstract
We present the results of simultaneous 450 μm and 850 μm polarization observations toward the massive star-forming region NGC 2071IR, a target of the BISTRO (B-fields in STar-forming Region Observations) Survey, using the POL-2 polarimeter and SCUBA-2 camera mounted on the James Clerk Maxwell Telescope. We find a pinched magnetic field morphology in the central dense core region, which could be due to a rotating toroidal disklike structure and a bipolar outflow originating from the central young stellar object IRS 3. Using the modified Davis–Chandrasekhar–Fermi method, we obtain a plane-of-sky magnetic field strength of 563 ± 421 μG in the central ∼0.12 pc region from 850 μm polarization data. The corresponding magnetic energy density of 2.04 × 10−8 erg cm−3 is comparable to the turbulent and gravitational energy densities in the region. We find that the magnetic field direction is very well aligned with the whole of the IRS 3 bipolar outflow structure. We find that the median value of polarization fractions is 3.0% at 450 μm in the central 3′ region, which is larger than the median value of 1.2% at 850 μm. The trend could be due to the better alignment of warmer dust in the strong radiation environment. We also find that polarization fractions decrease with intensity at both wavelengths, with slopes, determined by fitting a Rician noise model of 0.59 ± 0.03 at 450 μm and 0.36 ± 0.04 at 850 μm, respectively. We think that the shallow slope at 850 μm is due to grain alignment at the center being assisted by strong radiation from the central young stellar objects.
- Published
- 2021
- Full Text
- View/download PDF
5. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2: a case report
- Author
-
Chua, Gilbert T, primary, Wong, Joshua SC, additional, Chung, Jaime, additional, Lam, Ivan, additional, Kwong, Joyce, additional, Leung, Kate, additional, Law, CY, additional, Lam, CW, additional, Kwok, Janette, additional, Chu, Patrick WK, additional, Au, Elaine YL, additional, Lam, Crystal K, additional, Mak, Daniel, additional, Fong, NC, additional, Leung, Daniel, additional, Wong, Wilfred HS, additional, Ho, Marco HK, additional, Tsao, Sabrina SL, additional, Wong, Christina S, additional, Yam, Jason C, additional, Tso, Winnie WY, additional, To, Kelvin KW, additional, Tam, Paul KH, additional, Chan, Godfrey CF, additional, Leung, WH, additional, Yuen, KY, additional, Novelli, Vas, additional, Klein, Nigel, additional, Levin, Michael, additional, Whitaker, Elizabeth, additional, Lau, YL, additional, Ip, Patrick, additional, and Kwan, Mike YW, additional
- Published
- 2022
- Full Text
- View/download PDF
6. Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience
- Author
-
Fan Ky, Law Cy, Mok Ns, Y K Chong, CK Ching, Tak-cheung Yung, H H C Lee, Ching-Wan Lam, N C Fong, P T Tsui, Poon Wt, Yuet-Ping Yuen, Wai-Kwan Siu, Sammy Pak-Lam Chen, Chloe Mak, and Yan-Wo Chan
- Subjects
Adult ,Male ,0301 basic medicine ,Heterozygote ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Genetic counseling ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Catecholaminergic polymorphic ventricular tachycardia ,LMNA ,Electrocardiography ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Genetic Testing ,Child ,Genetic testing ,Brugada syndrome ,Aged, 80 and over ,medicine.diagnostic_test ,Genetic heterogeneity ,business.industry ,Infant ,General Medicine ,Middle Aged ,medicine.disease ,Arrhythmogenic right ventricular dysplasia ,Phenotype ,030104 developmental biology ,Mutation ,Hong Kong ,Channelopathies ,Female ,Cardiomyopathies ,business - Abstract
INTRODUCTION Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.
- Published
- 2018
7. Assessing the knowledge of private university students on self-medication practices, Malaysia
- Author
-
Pandian, BGanesh, primary, Sireesha, P, additional, Ng, YP, additional, Raj, SDevan, additional, Law, CY, additional, and Patrick, C. E. M, additional
- Published
- 2019
- Full Text
- View/download PDF
8. A Study on Trauma Documentation in Accident and Emergency Attendance Records
- Author
-
Law, CY, primary, Wong, TW, additional, and Lau, CC, additional
- Published
- 2006
- Full Text
- View/download PDF
9. A missense variant in SLC12A3 gene enhances aberrant splicing causing Gitelman syndrome.
- Author
-
Law CY, Lui DTW, Lau E, Woo CSL, Chang JYC, Leung EKH, Lee ACH, Lee CH, Woo YC, Chow WS, Lam KSL, Tan KCB, Ling TK, and Lam CW
- Subjects
- Humans, Female, RNA Splicing genetics, Adult, Gitelman Syndrome genetics, Solute Carrier Family 12, Member 3 genetics, Mutation, Missense
- Abstract
Gitelman syndrome (GS) is the most prevalent genetic tubulopathy characterized by several electrolyte abnormalities, including hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. These features are caused by a bi-allelic mutation in the SLC12A3 gene. In this report, we present a case of GS in an asymptomatic woman who incidentally exhibited hypokalemia during an antenatal check-up. Her biochemical profile was consistent with GS. Genetic analysis revealed two heterozygous variants in trans, namely, NM_001126108.2:c.625C>T; p.(Arg209Trp) and c.965C>T; p.(Ala322Val). The c.625C>T; p.(Arg209Trp) variant has previously been experimentally confirmed as a loss-of-function (LOF) variant. However, the functional impact of the c.965C>T variant, located at the 5 prime end of exon 8, has not been fully elucidated. Through the utilization of both complementary DNA (cDNA) and minigene analysis, we confirmed that the c.965C>T variant can generate two distinct cDNA transcripts. The first transcript carries a missense mutation, p.(Ala322Val) in the full SLC12A3 transcript, while the second transcript consists of an in-frame deletion of both exons 7 and 8 in the SLC12A3 transcript, in which may result in the loss of transmembrane regions 5 - 6 involved in chloride transport. Our findings provide insights into the intricate mechanisms of splicing, highlighting how a variant in one exon can remotely influence the transcription of an upstream exon, as observed with the variant in exon 8 impacting the transcription of exon 7., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2025
- Full Text
- View/download PDF
10. Allan-Herndon-Dudley syndrome in Hong Kong: Implication for newborn screening.
- Author
-
Yiu RS, Ling TK, Ko CH, Poon SW, Poon GW, Wong FC, Law CY, Iwayama H, and Lam CW
- Subjects
- Infant, Newborn, Male, Humans, Child, Hong Kong, Neonatal Screening, Monocarboxylic Acid Transporters genetics, Thyrotropin, Dystonia, Symporters genetics
- Abstract
Background: Allan-Herndon-Dudley syndrome (MCT 8 deficiency) is an X-linked recessive condition caused by hemizygous pathogenic variants in SLC16A2 encoding the monocarboxylate transporter 8 (MCT8). Patients present with global developmental delay and neurological impairment, and abnormal serum thyroid function tests. The drug, 3,3',5 triiodothyroacetic acid (TRIAC), was recently demonstrated to improve the endocrinological profile. Improvement in diagnostic approach is key to earlier start of treatment., Patient Findings: We described four Chinese patients with MCT8 deficiency undergoing different diagnostic odysseys. Their initial presentation included global developmental delay and dystonia. Patient 2 also had epilepsy. Patients 1 and 2 presented with two novel variants: (1)hemizygous NM_006517.4(SLC16A2):c.1170 + 2 T > A; p.(?), and (2)hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17) respectively. Patients 3 and 4 were biological brothers harboring hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17), which was first reported in 2004. We obtained the measurement of triiodothyronine (T3) and reverse T3 (rT3) from dried blood spot samples collected on Day 1 of life from Patient 1 and studied the biomarkers (rT3 and T3/rT3 ratio) proposed by Iwayama et al. for the detection of MCT8 deficiency at birth. Our data verified the significantly reduced rT3 level in Patient 1, compared with healthy newborns, although low T3 level and comparable T3/rT3 ratio with controls were detected., Summary: Patients with MCT8 deficiency often undergo diagnostic odysseys. An early diagnosis could be missed by a normal newborn thyroid function screening result based on biochemical measurement of TSH and/or T4/fT4. Early detection of rT3 is key to improving current diagnostic approach., Conclusion: We recommend that full thyroid function profile (TSH, T4/fT4, T3/fT3, rT3) be considered early for all pediatric patients presenting with unexplained developmental delay and/or dystonia. The potential inclusion of rT3 measurement in newborn screening may prove promising., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
11. A curious case of early-onset dementia.
- Author
-
Ip WCT, Shea YF, Ling TK, Law CY, Lam CW, and Chiu PKC
- Subjects
- Humans, Dementia etiology
- Abstract
Competing Interests: The authors have no conflicts of interest to disclose.
- Published
- 2023
- Full Text
- View/download PDF
12. A prospective follow-up on thyroid function, thyroid autoimmunity and long COVID among 250 COVID-19 survivors.
- Author
-
Lui DTW, Tsoi KH, Lee CH, Cheung CYY, Fong CHY, Lee ACH, Tam AR, Pang P, Ho TY, Law CY, Lam CW, To KKW, Chow WS, Woo YC, Hung IFN, Tan KCB, and Lam KSL
- Subjects
- Male, Humans, Middle Aged, Female, Autoimmunity, Post-Acute COVID-19 Syndrome, Follow-Up Studies, Prospective Studies, SARS-CoV-2, Interferons, Survivors, COVID-19, Thyroid Diseases
- Abstract
Purpose: We evaluated the evolution of thyroid function and autoimmunity among COVID-19 survivors over 6 months in relation to interferon beta-1b treatment and long COVID., Methods: We included COVID-19 survivors managed in a major COVID-19 centre between July 2020 and May 2021 who were reassessed three and/or six months after acute COVID-19. Thyroid function tests (TFTs) and anti-thyroid antibody titres were measured at acute COVID-19, 3-month and 6-month., Results: 250 COVID-19 survivors were included (mean age 52.7 years, 50.4% men). Persistent thyroid function abnormalities were more likely in those with abnormal TFTs in acute COVID-19 (P < 0.001). Among 51 patients with abnormal TFTs in acute COVID-19, 82.4% resolved upon follow-up. Of 199 patients with normal TFTs in acute COVID-19, only 4.5% had incident abnormal TFTs, more likely in interferon-treated patients (P = 0.044) and none clinically overt. Among 129 patients with complete 6-month follow-up for anti-thyroid antibody titres, there was no significant change overall, except for modest increase in anti-thyroid antibody titres among the 84 interferon-treated patients (P < 0.05 at both 3 months and 6 months). Long COVID occurred in 19.5% and 10.4% at 3 and 6 months respectively, where TFTs and anti-thyroid antibody titres were not predictive of its occurrence., Conclusion: Over 6 months, most abnormal TFTs in acute COVID-19 resolved, with no significant incident thyroid dysfunction. SARS-CoV-2 infection did not lead to change in thyroid autoimmunity, while interferon treatment was associated with modest increase in anti-thyroid antibody titres. Thyroid function and anti-thyroid antibodies did not play a significant role in long COVID., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
13. A prospective follow-up of thyroid volume and thyroiditis features on ultrasonography among survivors of predominantly mild to moderate COVID-19.
- Author
-
Fung MHM, Lui DTW, Chiu KWH, Lee SH, Lee CH, Chow WS, Lee ACH, Tam AR, Pang P, Ho TY, Fong CHY, Loong CHN, Law CY, To KKW, Lam CW, Tan KCB, Woo YC, Hung IFN, Lam KSL, and Lang B
- Subjects
- Adult, Male, Humans, Middle Aged, Female, Follow-Up Studies, SARS-CoV-2, Prospective Studies, Ultrasonography, Survivors, COVID-19 diagnostic imaging, Thyroiditis
- Abstract
Background: We previously showed that higher SARS-CoV-2 viral load correlated with smaller thyroid volumes among COVID-19 survivors at 2 months after acute COVID-19. Our current follow-up study evaluated the evolution of thyroid volumes and thyroiditis features within the same group of patients 6 months later., Methods: Adult COVID-19 survivors who underwent thyroid ultrasonography 2 months after infection (USG1) were recruited for follow-up USG 6 months later (USG2). The primary outcome was the change in thyroid volume. We also reassessed thyroiditis features on USG, thyroid function and anti-thyroid antibodies., Results: Fifty-four patients were recruited (mean age 48.1 years; 63% men). The mean thyroid volume increased from USG1 to USG2 (11.9 ± 4.8 to 14.5 ± 6.2 mL, p < 0.001). Thirty-two patients (59.3%) had significant increase in thyroid volume by ≥15%, and they had a median increase of +33.3% (IQR: +20.0% to +45.0%). Multivariable logistic regression analysis showed that only higher baseline SARS-CoV-2 viral load independently correlated with significant thyroid volume increase on USG2 ( p = 0.022). Among the seven patients with thyroiditis features on USG1, six (85.7%) had the features resolved on USG2. None had new thyroiditis features on USG2. All abnormal thyroid function during acute COVID-19 resolved upon USG1 and USG2., Conclusion: Most COVID-19 survivors had an increase in thyroid volume from early convalescent phase to later convalescent phase. This increase correlated with high initial SARS-CoV-2 viral load. Together with the resolution of thyroiditis features, these may suggest a transient direct atrophic effect of SARS-CoV-2 on the thyroid gland with subsequent recovery of thyroid volume and thyroiditis features., Competing Interests: The authors declare there are no competing interests., (©2023 Fung et al.)
- Published
- 2023
- Full Text
- View/download PDF
14. Activation of Brain Regions Associated with Working Memory and Inhibitory Control in Patients with Attention-Deficit/Hyperactivity Disorder in Functional Near-Infrared Spectroscopy: A Systematic Review.
- Author
-
Hou L, Yang J, Xu L, Peng J, Joyce Law CY, and Chen T
- Subjects
- Humans, Memory, Short-Term physiology, Spectroscopy, Near-Infrared methods, Prefrontal Cortex, Brain diagnostic imaging, Attention Deficit Disorder with Hyperactivity diagnostic imaging, Attention Deficit Disorder with Hyperactivity psychology
- Abstract
Introduction: Patients with attention-deficit/hyperactivity disorder (ADHD) often show abnormalities related to cognitive activities, especially related to working memory and inhibitory control. Functional near-infrared spectroscopy (fNIRS) is a non-invasive brain imaging technique based on the changes in cerebral hemodynamics to measure the response of brain activities to cognitive tasks., Methods: In this review, we collected all clinical experiments that evaluated the changes of oxyhemoglobin levels in relevant brain regions of patients with ADHD through cognitive tasks by fNIRS to determine the abnormalities of brain regions related to working memory and inhibitory control activities in patients with ADHD., Results: From the beginning of November 2021, PubMed, PsycINFO, Scopus, EMBASE, CINAHL, web of science and Cochrane library were searched, and ROBINS-I was a tool to evaluate the quality and risk bias of the articles included. Sixteen eligible clinical trials or randomized controlled trials were included, of which six measured working memory and eleven measured inhibitory control., Conclusion: We found that compared with healthy people, the activation scope of working memory and inhibition control in the frontal cortex in ADHD patients was smaller than that in healthy people, and the activation degree was weak or even inactive, which can provide new ideas for the direction of research on ADHD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
- Full Text
- View/download PDF
15. Case Report: Prenatal Recurrent Microcephaly and Corpus Callosum Abnormalities in a Chinese Family with Novel Biallelic SASS6 Mutations.
- Author
-
Wah YMI, Cao Y, Law CY, Choy KW, Leung TY, Kwan HWA, and Poon LC
- Subjects
- Female, Humans, Pregnancy, Cell Cycle Proteins genetics, Corpus Callosum diagnostic imaging, Corpus Callosum pathology, East Asian People, Mutation, Pedigree, Prenatal Diagnosis, Microcephaly diagnostic imaging, Microcephaly genetics
- Abstract
Introduction: Primary microcephaly (MCPH) is not an uncommon disorder with multiple etiologies. There are a growing number of MCPH-related genes discovered due to the extensive application of whole-exome sequencing (WES) in clinical and research settings. Biallelic mutations in the SASS6 gene cause an extremely rare MCPH, type 14. To date, only two families with SASS6 gene-related microcephaly have been reported., Case Description: We report a case of recurrent congenital microcephaly in a Chinese family. The two affected fetuses presented with microcephaly early in the second trimester with agenesis of the corpus callosum. In the first affected fetus, trio WES detected two compound heterozygous candidate variants c.1139T>C(p.L380P) and c.1223C>G (p.T408S) in the SASS6 gene. Another affected fetus also inherited both variants, while the normal child carried neither variant through Sanger sequencing analysis. Both variants were classified as a variant of uncertain significance according to the current American College of Medical Genetics and Genomics guidelines., Conclusion: We reported novel biallelic variants in the SASS6 gene, encoding the SAS6 centriolar assembly protein, associated with prenatal onset of autosomal recessive microcephaly. We postulate that the pathomechanism of the compound heterozygous variants in close proximity could potentiate the overall coiled instability leading to the phenotypic features of our case., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
- Full Text
- View/download PDF
16. Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.
- Author
-
Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Cheung CYY, Fong CHY, Kwok STM, Law CY, To KKW, Lam CW, Tan KCB, Woo YC, Hung IFN, and Lam KSL
- Subjects
- C-Reactive Protein, Female, Humans, Male, Middle Aged, SARS-CoV-2, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, COVID-19 diagnosis, COVID-19 epidemiology, Triiodothyronine
- Abstract
Purpose: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients., Methods: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria., Results: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients., Conclusion: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)
- Published
- 2022
- Full Text
- View/download PDF
17. C-terminal truncated SPOP, a Janus-faced variant, causing a mixed type 1 and type 2 Nabais Sa-de Vries syndrome.
- Author
-
Law CY and Lam CW
- Subjects
- Humans, Intellectual Disability genetics, Mutation, Missense, Phenotype, Syndrome, Genes, Dominant genetics, Neurodevelopmental Disorders genetics, Nuclear Proteins genetics, Repressor Proteins genetics
- Abstract
Nabais Sa-de Vries syndrome (NSDVS) is an autosomal dominant neurodevelopmental disorder first described in 2020 and is classified into type 1 (NSDVS1) and type 2 (NSDVS2) which encompassed of spectrum of distinct clinical features due to gain-of-function (GOF) and loss-of-function (LOF) variants respectively. So far only 6 cases of 5 different missense pathogenic variants had been reported which impact on the SPOP substrate binding affinity for the downstream ubiquitylation. Here, we report a novel and de novo heterozygous nonsense pathogenic variant, p.Tyr353Term at the BACK domain in a patient with neurodevelopmental delay plus mixed phenotypes of NSDVS type 1 and 2 using trio exome analysis. The BACK domain is functionally critical for the SPOP higher-order oligomerization and is shown to increase substrate binding avidity with enhanced ubiquitylation efficiency in vitro. Experimentally, a missense variant p.Tyr353Glu is proven to attenuate the tandem SPOP oligomer formation and we envisage the current truncated variant at the same residue would attenuate the oligomerization process. This is the first report providing in vivo clue about the clinical significance of SPOP oligomerization in human neurodevelopmental disorders with new understanding on the expanding spectrum of NSDVS. We conclude the p.Tyr353Term is a Janus-faced variant which explains the dual NSDVS type 1 and 2 phenotypes in this case., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
18. Nuclear magnetic resonance spectroscopy-based urinalysis for a young girl with extreme hypoglycaemia.
- Author
-
Law CY, Kwok AM, Ling TK, Wong KC, Lau NK, Poon GW, and Lam CW
- Subjects
- Female, Humans, Magnetic Resonance Spectroscopy, Hypoglycemia diagnosis, Urinalysis
- Published
- 2022
- Full Text
- View/download PDF
19. Changing pleural fluid triglyceride levels in cirrhotic chylothorax.
- Author
-
Chan KP, Yip WH, Chan TYC, and Law CY
- Abstract
Chylothorax is an uncommon disease entity, but it occasionally poses a diagnostic challenge to physicians. Pleural fluid triglyceride level has been advocated as a screening test to diagnose chylothorax. However, its level can be depressed if there is an additional pathology driving the process of pleural fluid production. We report a case of high-volume pleural fluid output due to dual pathologies, cirrhotic hydrothorax and chylothorax, causing an initial failure to diagnose chylothorax due to low pleural fluid triglyceride level. The fluid triglyceride levels were unmasked after the treatment for underlying portal hypertension. These findings were further substantiated by positive lipoprotein electrophoresis for chylomicron. In this patient, lipoprotein electrophoresis of his pleural fluid specimen helps distinguish chylothorax as a second pathology amidst the underlying cirrhotic hydrothorax., Competing Interests: None declared., (© 2022 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)
- Published
- 2022
- Full Text
- View/download PDF
20. Serum ceruloplasmin monitoring in a case of silver intoxication due to intravenous silver infusion.
- Author
-
Law CY, Leung SC, Loong F, Ling TK, Wong KC, Lau NK, Tsui SH, Lai CL, and Lam CW
- Subjects
- Copper metabolism, Humans, Liver metabolism, Liver Function Tests, Male, Middle Aged, Ceruloplasmin metabolism, Silver metabolism
- Abstract
Introduction: Colloidal silver packaged as a dietary supplement is readily available online and is thought to be safe. Literature describing its toxicity in humans is scarce., Case Report: A 47-year-old man presented to us for sensory and gait problems. He had unremarkable past health except dystrophic nails. He further volunteered a history of receiving chronic oral and intravenous administration of colloidal silver. We confirmed his plasma silver was 1200-fold elevated, measuring 11990 nmol/L (normal < 10 nmol/L). He had deranged liver function tests, and liver biopsy showed distorted acinar architecture, bridging fibrosis and lymphocytic infiltrate with silver particles clustering along the vascular endothelium and portal venules. Brain magnetic resonance imagining showed features of mineralization over bilateral globus pallidi. There was biochemical evidence of central adrenal insufficiency, intracellular iron overload and hypoceruloplasminemia (<0.05 g/L). Gradual clinical and biochemical improvement was noted after silver cessation: his plasma silver dropped to 4800 nmol/L (3 months) and 1650 nmol/L (12 months), and serum ceruloplasmin reverted to 0.13 g/L (10 months) and 0.29 g/L (20 months)., Conclusions: The potential effects of silver to liver and copper metabolism were shown in this case. Serum ceruloplasmin also serves as a surrogate marker in monitoring silver intoxication.
- Published
- 2022
- Full Text
- View/download PDF
21. The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients.
- Author
-
Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Pang P, Ho TY, Cheung CYY, Fong CHY, Law CY, To KKW, Lam CW, Tan KCB, Woo YC, Hung IFN, and Lam KSL
- Subjects
- Adult, Aged, COVID-19 virology, China epidemiology, Female, Hospitalization, Humans, Lymphocyte Count, Lymphopenia blood, Lymphopenia immunology, Lymphopenia virology, Male, Middle Aged, Thyroid Diseases blood, Thyroid Diseases immunology, Thyroid Diseases virology, Thyroid Function Tests, Thyroid Hormones blood, COVID-19 complications, Lymphocytes pathology, Lymphopenia epidemiology, SARS-CoV-2 isolation & purification, Thyroid Diseases epidemiology, Thyrotropin blood, Triiodothyronine blood
- Abstract
Background: Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated., Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission., Results: A total of 541 patients were included. Median LYM was 1.22 x 10
9 /L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001)., Conclusion: TSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lui, Lee, Chow, Lee, Tam, Pang, Ho, Cheung, Fong, Law, To, Lam, Tan, Woo, Hung and Lam.)- Published
- 2022
- Full Text
- View/download PDF
22. Higher SARS-CoV-2 viral loads correlated with smaller thyroid volumes on ultrasound among male COVID-19 survivors.
- Author
-
Lui DTW, Fung MMH, Chiu KWH, Lee CH, Chow WS, Lee ACH, Tam AR, Pang P, Ho TY, Fong CHY, Loong CHN, Wong WW, Lee CYY, Law CY, To KKW, Lam CW, Tan KCB, Woo YC, Hung IFN, Lam KSL, and Lang BHH
- Subjects
- Adult, Female, Humans, Male, SARS-CoV-2, Survivors, Ultrasonography, Viral Load, COVID-19, Thyroiditis
- Abstract
Purpose: Thyroid dysfunction, including thyroiditis, is well recognized in COVID-19 patients. We evaluated thyroid ultrasonographic features among COVID-19 survivors, which are less well known., Methods: Adult COVID-19 survivors without known thyroid disorders who attended dedicated COVID-19 clinic underwent thyroid ultrasonography and assessment of thyroid function and autoimmunity. Adults admitted for acute non-thyroidal surgical problems and negative for COVID-19 were recruited as control. SARS-CoV-2 viral load (VL) was presented as the inverse of cycle threshold values from the real-time reverse transcription-polymerase chain reaction of the respiratory specimen on admission., Results: In total, 79 COVID-19 patients and 44 non-COVID-19 controls were included. All abnormal thyroid function tests during acute COVID-19 recovered upon follow-up. Thyroid ultrasonography was performed at a median of 67 days after acute COVID-19. The median thyroid volume was 9.73 mL (IQR: 7.87-13.70). In multivariable linear regression, SARS-CoV-2 VL on presentation (standardized beta -0.206, p = 0.042) inversely correlated with thyroid volume, in addition to body mass index at the time of ultrasonography (p < 0.001). Sex-specific analysis revealed similar results among men but not women. Eleven COVID-19 patients (13.9%) had ultrasonographic changes suggestive of thyroiditis, comparable to non-COVID-19 patients (p = 0.375). None of these 11 patients had isolated low thyroid-stimulating hormone levels suggestive of thyroiditis at initial admission or the time of ultrasonography., Conclusions: Higher SARS-CoV-2 VL on presentation were associated with smaller thyroid volumes, especially in men. Further research is suggested to investigate this possible direct viral effect of SARS-CoV-2 on the thyroid gland. There was no increased rate of ultrasonographic features suggestive of thyroiditis in COVID-19 survivors., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2021
- Full Text
- View/download PDF
23. Correction: Oleanolic acid enhances neural stem cell migration, proliferation and differentiation in vitro by inhibiting GSK3β activity.
- Author
-
Zhang SQ, Lin KL, Law CY, Liu B, Fu XQ, Tse WS, Wong SSM, Sze SCW, and Yung KKL
- Published
- 2021
- Full Text
- View/download PDF
24. Urine organic acid as the first clue towards aromatic L-amino acid decarboxylase (AADC) deficiency in a high prevalence area.
- Author
-
Ling TK, Wong KC, Chan CY, Lau NK, Law CY, Lee HH, Lai CK, Chong YK, Yau KE, Cheung KM, Ko CH, Fung CW, Lee LK, Wong SS, Mak CM, Chan AY, Tam S, and Lam CW
- Subjects
- Aromatic-L-Amino-Acid Decarboxylases deficiency, Aromatic-L-Amino-Acid Decarboxylases genetics, Humans, Prevalence, Retrospective Studies, Amino Acid Metabolism, Inborn Errors diagnosis, Amino Acid Metabolism, Inborn Errors epidemiology, Amino Acid Metabolism, Inborn Errors genetics
- Abstract
Background: Aromatic L-amino acid decarboxylase deficiency is a rare neurometabolic disease due to impaired decarboxylation of neurotransmitter precursors to its active form., Case: We retrospectively reviewed 8 cases from 2008 to 2019 with cerebrospinal fluid neurotransmitter analysis performed at our centre. All cases had an elevated urine vanillactic acid and, in most cases, with N-acetylvanilalanine detected. Cerebrospinal fluid analysis showed low downstream metabolites vanillylmandelic acid, homovanillic acid but high 3-O-methyl-L-DOPA, 5-hydroxytryptophan. Cerebrospinal fluid pterins were normal. Genotyping in DDC confirms the diagnosis. Urine organic acid analysis provided the first clue to diagnosis in four of the cases, which then triggered cerebrospinal fluid neurotransmitter and genetic analysis. We also developed a diagnostic decision support system to assist the interpretation of the mass spectrometry data from urine organic acids., Conclusions: Urine organic acid could be essential in guiding subsequent investigations for the diagnosis of aromatic L-amino acid decarboxylase deficiency. We propose to screen suspected cases first with urine organic acids, specifically looking for vanillactic acid and N-acetylvanilalanine. Suggestive findings should be followed with target analysis for c.714 + 4A > T in ethnically Chinese patients. The assistive tool allowed expedite interpretation of profile data generated from urine organic acids analysis. It may also reduce interpreter's bias when peaks of interest are minor peaks in the spectrum., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
25. The Impact of Interferon Beta-1b Therapy on Thyroid Function and Autoimmunity Among COVID-19 Survivors.
- Author
-
Lui DTW, Hung IFN, Lee CH, Lee ACH, Tam AR, Pang P, Ho TY, Cheung CYY, Fong CHY, Law CY, To KKW, Lam CW, Chow WS, Woo YC, Lam KSL, and Tan KCB
- Subjects
- Adult, Antibodies analysis, Cohort Studies, Female, Follow-Up Studies, Humans, Immunoglobulins, Thyroid-Stimulating analysis, Male, Middle Aged, Survivors, Thyroid Diseases immunology, Thyrotropin blood, Thyroxine blood, Triiodothyronine blood, Autoimmunity drug effects, COVID-19 immunology, Interferon beta-1b adverse effects, Interferon beta-1b therapeutic use, Thyroid Diseases chemically induced, Thyroid Function Tests, Thyroid Gland drug effects, COVID-19 Drug Treatment
- Abstract
Background: Some studies have indicated that interferon (IFN) may be valuable in COVID-19. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors., Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured both on admission and at three months., Results: 226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. There tended to be more abnormal TFTs upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). 179 patients (65.4% IFN-treated) had a complete reassessment of anti-thyroid antibodies. There were significant increases in titres of both anti-thyroid peroxidase antibodies (anti-TPO: baseline 29.21 units [IQR: 14.97 - 67.14] vs reassessment 34.30 units [IQR: 18.82 - 94.65], p<0.001) and anti-thyroglobulin antibodies (anti-Tg: baseline 8.23 units [IQR: 5.40 - 18.44] vs reassessment 9.14 units [IQR: 6.83 - 17.17], p=0.001) in the IFN-treated group but not IFN-naïve group. IFN treatment (standardised beta 0.245, p=0.001) was independently associated with changes in anti-TPO titre. Of the 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive upon reassessment (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025)., Conclusion: IFN for COVID-19 was associated with modest increases in anti-thyroid antibody titres, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence. Our findings suggest that clinicians monitor the thyroid function and anti-thyroid antibodies among IFN-treated COVID-19 survivors, and call for further follow-up studies regarding the clinical significance of these changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lui, Hung, Lee, Lee, Tam, Pang, Ho, Cheung, Fong, Law, To, Lam, Chow, Woo, Lam and Tan.)
- Published
- 2021
- Full Text
- View/download PDF
26. Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?
- Author
-
Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Pang P, Ho TY, Fong CHY, Law CY, Leung EKH, To KKW, Tan KCB, Woo YC, Lam CW, Hung IFN, and Lam KSL
- Subjects
- Adult, Female, Humans, Male, Middle Aged, SARS-CoV-2, Thyroid Gland, Post-Acute COVID-19 Syndrome, Autoimmunity, COVID-19 complications
- Abstract
Objective: Post-acute sequelae of coronavirus disease 2019 (COVID-19) or long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC., Methods: We included consecutive adults without a known thyroid disorder who were admitted to a major COVID-19 center for confirmed COVID-19 from July to December 2020. Thyroid function tests and antithyroid antibodies were measured for all patients on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up., Results: In total, 204 patients (median age, 55.0 years; 95 men [46.6%]) were reassessed at a median of 89 days (interquartile range, 69-99) after acute COVID-19. Of the 204 patients, 41 (20.1%) had LC. Female sex (adjusted odds ratio, 2.48; P = .018) and severe acute respiratory syndrome coronavirus 2 polymerase chain reaction cycle threshold value of <25 on admission (adjusted odds ratio, 2.84; P = .012) independently predicted the occurrence of LC. Upon follow-up, most abnormal thyroid function tests in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident antithyroid peroxidase (anti-TPO) positivity. Although baseline or follow-up thyroid function tests were not associated with the occurrence of LC, among 172 patients with symptomatic acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (P = .043)., Conclusion: LC is common among COVID-19 survivors, with females and those with higher viral load in acute COVID-19 particularly being vulnerable. The observation of incident anti-TPO positivity warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in LC remains to be elucidated., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
27. Role of non-thyroidal illness syndrome in predicting adverse outcomes in COVID-19 patients predominantly of mild-to-moderate severity.
- Author
-
Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Fong CHY, Law CY, Leung EKH, To KKW, Tan KCB, Woo YC, Lam CW, Hung IFN, and Lam KSL
- Subjects
- Adult, Humans, Middle Aged, Prospective Studies, SARS-CoV-2, Triiodothyronine, Viral Load, COVID-19, Euthyroid Sick Syndromes
- Abstract
Objective: Existing studies reported the potential prognostic role of non-thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid-stimulating hormone (TSH), mainly in severe COVID-19. None considered the significant impact of SARS-CoV-2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild-to-moderate COVID-19 patients., Design: A prospective study of COVID-19 patients., Patients and Measurements: Consecutive adults admitted to Queen Mary Hospital for confirmed COVID-19 from July to December 2020 were prospectively recruited. SARS-CoV-2 viral load was represented by cycle threshold (Ct) values from real-time reverse transcription-polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline., Results: We recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty-three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS-CoV-2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration (p < .001). In multivariable stepwise logistic regression analysis, NTIS independently predicted clinical deterioration (adjusted odds ratio 3.19, p = .017), in addition to Ct value <25 (p < .001), elevated C-reactive protein (p = .004), age >50 years (p = .011) and elevated creatine kinase (p = .017)., Conclusions: Non-thyroidal illness syndrome was not uncommon even in mild-to-moderate COVID-19 patients. NTIS on admission could predict clinical deterioration in COVID-19, independent of SARS-CoV-2 viral load, age and markers of inflammation and tissue injury., (© 2021 John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
28. Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors.
- Author
-
Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Fong CHY, Law CY, Leung EKH, To KKW, Tan KCB, Woo YC, Lam CW, Hung IFN, and Lam KSL
- Subjects
- Adult, Autoimmunity physiology, COVID-19 complications, COVID-19 immunology, China epidemiology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Patient Admission statistics & numerical data, Prospective Studies, SARS-CoV-2 physiology, Thyroid Diseases etiology, Thyroid Function Tests, Thyroiditis, Autoimmune epidemiology, Thyroiditis, Autoimmune etiology, COVID-19 epidemiology, Survivors statistics & numerical data, Thyroid Diseases epidemiology, Thyroid Gland immunology, Thyroid Gland physiology
- Abstract
Background: The occurrence of Graves' disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors., Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months., Results: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer., Conclusion: Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.
- Published
- 2021
- Full Text
- View/download PDF
29. Thyroid Dysfunction in Relation to Immune Profile, Disease Status, and Outcome in 191 Patients with COVID-19.
- Author
-
Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Fong CHY, Law CY, Leung EKH, To KKW, Tan KCB, Woo YC, Lam CW, Hung IFN, and Lam KSL
- Subjects
- Adult, Aged, Aged, 80 and over, COVID-19 complications, COVID-19 epidemiology, COVID-19 immunology, Cohort Studies, Euthyroid Sick Syndromes complications, Euthyroid Sick Syndromes diagnosis, Euthyroid Sick Syndromes epidemiology, Euthyroid Sick Syndromes immunology, Female, Humans, Immune System physiopathology, Male, Middle Aged, Prognosis, SARS-CoV-2 physiology, Severity of Illness Index, Thyroid Diseases complications, Thyroid Diseases epidemiology, Thyroid Function Tests, Thyroid Gland physiology, Thyroiditis, Autoimmune complications, Thyroiditis, Autoimmune diagnosis, Thyroiditis, Autoimmune epidemiology, Thyrotoxicosis complications, Thyrotoxicosis diagnosis, Thyrotoxicosis epidemiology, Thyrotoxicosis immunology, COVID-19 diagnosis, Immune System physiology, Thyroid Diseases diagnosis, Thyroid Diseases immunology
- Abstract
Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2-related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of coronavirus disease 2019 (COVID-19) patients, in relation to their clinical features, and biochemical, immunological, and inflammatory markers., Methods: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from July 21 to August 21, 2020, were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3), and antithyroid antibodies were measured on admission., Results: Among 191 patients with COVID-19 (mean age 53.5 ± 17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. Abnormal thyroid function was seen in 13.1%. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in 2 of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing nonthyroidal illness syndrome. Lower SARS-Cov-2 polymerase chain reaction cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (P = .030) and low fT3 (P = .007), respectively. A decreasing trend of fT3 with increasing COVID-19 severity (P = .032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes., Conclusion: Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
30. Novel PPOX exonic mutation inducing aberrant splicing in a patient with homozygous variegate porphyria.
- Author
-
Cho SY, Lau EY, Luk DC, Law CY, Lai CK, and Lam CW
- Subjects
- Exons genetics, Flavoproteins genetics, Humans, Mitochondrial Proteins genetics, Mutation, Protoporphyrinogen Oxidase genetics, Porphyria, Variegate genetics
- Abstract
Introduction: Variegate porphyria (VP; OMIM 176200) is one of the acute hepatic porphyrias, and it is characterized by the partial deficiency of protoporphyrinogen oxidase (PPOX). The unusual homozygous variant with mutations on both alleles of PPOX is distinguished with general heterozygous VP by several typical points such as severe defect in PPOX enzyme activity, early onset of photosensitivity before puberty, and skeletal deformity., Material and Method: In this study, we describe a very rare case of autosomal recessive form of true homozygous VP found in a Chinese patient with consanguineous parents. Sanger sequencing of the PPOX gene showed a novel homozygous variant located at the first base of exon 8 of the gene, i.e., NM_000309.3c.808G > T. To investigate aberrant splicing induced by the mutant, wild-type exon 8 and mutant exon 8 were expressed in pET01 vector as minigene in cultured-cells and analyzed by RT-PCR., Results: The wildtype PPOX showed an expected band in the gel electrophoresis after RT-PCR. The PPOX c.808G > T only showed a band similar to the band size of the vector only control. This result suggested c.808G > T mutant is an exonic mutation inducing aberrant splicing of pre-mRNA of the PPOX gene., Conclusion: This study showed a very rare case of homozygous VP with autosomal recessive homoallelic pattern. In comparison with previous cases of homozygous VP presenting brachydactyly, it is notable that our patient did not have any skeletal deformities., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
31. Centrosome-associated CDC25B is a novel disease-causing gene for a syndrome with cataracts, dilated cardiomyopathy, and multiple endocrinopathies.
- Author
-
Lam CW, Fong NC, Chan TY, Lau KC, Ling TK, Mak DW, Cheng X, and Law CY
- Subjects
- Centrosome, Female, Homozygote, Humans, Male, Pedigree, cdc25 Phosphatases, Cardiomyopathy, Dilated genetics, Cataract genetics
- Abstract
We describe a unique Chinese girl who presented with intrauterine growth retardation, delayed development, bilateral cataracts, hypothyroidism, growth hormone deficiency, and juvenile dilated cardiomyopathy. She was born to consanguineous parents with a history of one fetal and one infantile death in the family. She died from cardiac failure at the age of 12. In the pursuit of a diagnosis, the family was referred to the Clinics for Rare Diseases Referral and the University of Hong Kong Undiagnosed Disease Program. Whole-exome sequencing analysis revealed a homozygous non-sense variant, NM_021873:c.313G > T (p.Glu105*), in the CDC25B gene, a key regulator of the cell cycle. This variant was located in a region of homozygosity of 25 Mb on chromosome 20. Her parents and two asymptomatic sisters were confirmed to be carriers and one brother did not carry the variant. This is the first report of a natural human knockout of the CDC25B gene. Multiple endocrinopathies and fatal juvenile dilated cardiomyopathy suggests the potential for unfavorable complications in oncology patients receiving CDC25B inhibitors as an emerging targeted therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
32. Clinical whole-exome sequencing reveals a common pathogenic variant in patients with CoQ 10 deficiency: An underdiagnosed cause of mitochondriopathy.
- Author
-
Ling TK, Law CY, Yan KW, Fong NC, Wong KC, Lee KL, Chu WC, Brea-Calvo G, and Lam CW
- Subjects
- Ataxia metabolism, Ataxia pathology, Female, Genetic Variation genetics, Humans, Infant, Infant, Newborn, Male, Mitochondria metabolism, Mitochondrial Diseases metabolism, Mitochondrial Diseases pathology, Muscle Weakness metabolism, Muscle Weakness pathology, Mutation, Ubiquinone genetics, Ubiquinone metabolism, Ataxia diagnosis, Ataxia genetics, Mitochondria genetics, Mitochondria pathology, Mitochondrial Diseases diagnosis, Mitochondrial Diseases genetics, Muscle Weakness diagnosis, Muscle Weakness genetics, Ubiquinone deficiency, Exome Sequencing
- Abstract
Background: Primary CoQ deficiency occurs because of the defective biosynthesis of coenzyme Q, one of the key components of the mitochondrial electron transport chain. Patients with this disease present with a myriad of non-specific symptoms and signs, posing a diagnostic challenge. Whole-exome sequencing is vital in the diagnosis of these cases., Case: Three unrelated cases presenting as either encephalopathy or cardiomyopathy have been diagnosed to harbor a common pathogenic variant c.370G > A in COQ4. COQ4 encodes a key structural component for stabilizing the multienzymatic CoQ biosynthesis complex. This variant is detected only among East and South Asian populations., Conclusions: Based on the population data and our case series, COQ4-related mitochondriopathy is likely an underrecognized condition. We recommend including the COQ4 c.370G > A variant as a part of the screening process for mitochondriopathy in Chinese populations., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
33. Deoxythymidylate kinase, DTYMK, is a novel gene for mitochondrial DNA depletion syndrome.
- Author
-
Lam CW, Yeung WL, Ling TK, Wong KC, and Law CY
- Subjects
- Child, DNA, Mitochondrial genetics, Humans, Infant, Male, Siblings, Exome Sequencing, DNA, Mitochondrial metabolism, Mitochondrial Diseases enzymology, Mitochondrial Diseases genetics, Nucleoside-Phosphate Kinase genetics
- Abstract
Background: Mitochondrial DNA depletion syndrome is a group of heterogeneous diseases with non-specific presentation. The common feature is the quantitative depletion of mitochondrial DNA without qualitative defects. Diagnosis of these diseases poses a challenge and whole exome sequencing is often needed for their diagnoses., Case: Two siblings of a quartet family, presenting with hypotonia, microcephaly and severe intellectual disability, have been diagnosed to harbor two heterozygous variants in trans in the DTYMK gene of the thymidine biosynthesis pathway. Mitochondrial DNA depletion has been demonstrated in silico in the more severe sibling., Conclusions: We suggest the consideration of incorporating DTYMK as one of the associated genes of mitochondrial DNA depletion syndrome (MDDS). DTYMK may be the missing link in the mitochondrial nucleotide salvage pathway but further characterization and additional evidence would be needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
34. Gelsemium poisoning mediated by the non-toxic plant Cassytha filiformis parasitizing Gelsemium elegans.
- Author
-
Cheung WL, Law CY, Lee HCH, Tang CO, Lam YH, Ng SW, Chan SS, Chow TC, Pang KS, and Mak TWL
- Subjects
- Adult, Alkaloids metabolism, Chromatography, High Pressure Liquid, Gelsemium metabolism, Gelsemium parasitology, Humans, Lauraceae metabolism, Middle Aged, Tandem Mass Spectrometry, Young Adult, Alkaloids chemistry, Alkaloids poisoning, Gelsemium chemistry, Gelsemium poisoning, Lauraceae poisoning
- Abstract
Introduction: Gelsemium poisoning is caused by consumption of the deadly Gelsemium species such as Gelsemium elegans, leading to significant gastrointestinal, neurological and cardio-respiratory toxicities. In 2011 (Cluster 1) and 2012 (Cluster 2), the authors encountered two clusters of gelsemium poisoning after consumption of the non-toxic parasitic plant Cassytha filiformis. The current study aims to examine the mechanism of gelsemium poisoning mediated by a benign parasitic plant., Methods: Qualitative analysis of toxic gelsemium alkaloids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on the herbal and urine samples from both clusters to confirm exposure. Morphological examination, qualitative analysis of aporphine alkaloids using liquid chromatography-ion trap-time of flight mass spectrometry (LC-IT-TOF/MS) and Sanger sequencing were performed on the plant sample from Cluster 2 to confirm its identity. A field study was conducted in local countryside and C. filiformis was collected for histological, LC-MS/MS and LC-IT-TOF/MS analyses to study its interaction with G. elegans., Results: Gelsemium alkaloids that are not naturally present in C. filiformis were detected in the patients' herbal and urine samples. Misidentification and contamination with G. elegans during the preparation process were excluded by morphological examination of the plant sample from Cluster 2. Its identity as C. filiformis was verified with LC-IT-TOF/MS and molecular analyses. Histological, LC-MS/MS and LC-IT-TOF/MS analyses of C. filiformis collected during the field study confirmed that its haustoria penetrated the vascular bundles of G. elegans and absorbed its gelsemium toxins., Conclusions: The non-toxic plant C. filiformis absorbed toxic gelsemium alkaloids from its host, G. elegans, and led to gelsemium poisoning in our patients. Our study provides new insights into the toxicology of such plants. Benign parasitic plants may lead to potentially life-threatening poisoning if it parasitizes toxic hosts and absorbs their phytotoxins. The public awareness of risks associated with the use of these medicinal parasitic plants should be raised., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
35. Oleanolic acid enhances neural stem cell migration, proliferation, and differentiation in vitro by inhibiting GSK3β activity.
- Author
-
Zhang SQ, Lin KL, Law CY, Liu B, Fu XQ, Tse WS, Wong SSM, Sze SCW, and Yung KKL
- Abstract
Oleanolic acid (OA), one of the bioactive ingredients in ginseng, has been reported to have neuroprotective activities. However, the effects and its mechanism on neural stem cell (NSC) induction are not entirely clear. In the present study, we investigated the effects of OA on promoting the migration, proliferation, and differentiation of neural stem cells (NSCs). Migration and proliferation were investigated by using neural-specific markers, neurosphere assay, and Cell Counting Kit-8, respectively. We found OA remarkably promoted neural migration and proliferation of NSCs in a time- and dose-dependent manner. Differentiation was analyzed by western blotting and immunofluorescence staining, which found MAP2 expression was remarkably increased, whereas Nestin was dramatically decreased. In addition, OA increased phosphorylation of GSK3β at Ser9 and expression of active forms of β-catenin. Furthermore, NSCs with constitutively active GSK3β (S9A) significantly suppressed the OA-induced proliferation and neural differentiation. These results showed that OA could stimulate NSC proliferation and neural differentiation in vitro via suppressing the activity of GSK3β. Our findings may have significant implications for the treatment of neurodegenerative diseases., Competing Interests: The authors declare that they have no conflict of interest.
- Published
- 2018
- Full Text
- View/download PDF
36. Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.
- Author
-
Mak CM, Chen SP, Mok NS, Siu WK, Lee HH, Ching CK, Tsui PT, Fong NC, Yuen YP, Poon WT, Law CY, Chong YK, Chan YW, Yung TC, Fan KY, and Lam CW
- Subjects
- Adolescent, Adult, Aged, 80 and over, Child, Electrocardiography, Female, Heterozygote, Hong Kong, Humans, Infant, Male, Middle Aged, Mutation, Phenotype, Young Adult, Cardiomyopathies diagnosis, Cardiomyopathies genetics, Channelopathies diagnosis, Channelopathies genetics, Genetic Testing statistics & numerical data
- Abstract
Introduction: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015., Methods: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy., Results: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup)., Conclusions: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.
- Published
- 2018
- Full Text
- View/download PDF
37. Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.
- Author
-
Murmann AE, Gao QQ, Putzbach WE, Patel M, Bartom ET, Law CY, Bridgeman B, Chen S, McMahon KM, Thaxton CS, and Peter ME
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation genetics, Disease Models, Animal, Humans, Huntingtin Protein antagonists & inhibitors, Huntington Disease genetics, Huntington Disease pathology, Mice, Neoplasms pathology, Neoplasms therapy, Open Reading Frames, RNA, Small Interfering genetics, Trinucleotide Repeat Expansion genetics, Trinucleotide Repeats drug effects, Huntingtin Protein genetics, Neoplasms genetics, RNA, Small Interfering pharmacology, Trinucleotide Repeats genetics
- Abstract
Trinucleotide repeat (TNR) expansions in the genome cause a number of degenerative diseases. A prominent TNR expansion involves the triplet CAG in the huntingtin (HTT) gene responsible for Huntington's disease (HD). Pathology is caused by protein and RNA generated from the TNR regions including small siRNA-sized repeat fragments. An inverse correlation between the length of the repeats in HTT and cancer incidence has been reported for HD patients. We now show that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complementary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the six members in the CAG/CUG family of related TNRs are the most toxic to both human and mouse cancer cells. siCAG/CUG TNR-based siRNAs induce cell death in vitro in all tested cancer cell lines and slow down tumor growth in a preclinical mouse model of ovarian cancer with no signs of toxicity to the mice. We propose to explore TNR-based siRNAs as a novel form of anticancer reagents., (© 2018 The Authors.)
- Published
- 2018
- Full Text
- View/download PDF
38. Induction of DISE in ovarian cancer cells in vivo .
- Author
-
Murmann AE, McMahon KM, Haluck-Kangas A, Ravindran N, Patel M, Law CY, Brockway S, Wei JJ, Thaxton CS, and Peter ME
- Abstract
The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. shRNAs and siRNAs derived from CD95 or CD95 ligand (CD95L) are highly toxic to most cancer cells. We recently found that these sh/siRNAs kill cancer cells in the absence of the target by targeting the 3'UTRs of critical survival genes through canonical RNAi. We have named this unique form of off-target effect DISE (for death induced by survival gene elimination). DISE preferentially kills transformed cells and cancer stem cells. We demonstrate that DISE induction occurs in cancer cells in vivo after introducing a lentiviral CD95L derived shRNA (shL3) into HeyA8 ovarian cancer cells grown as i.p. xenografts in mice, when compared to a scrambled shRNA. To demonstrate the possibility of therapeutically inducing DISE, we coupled siRNAs to templated lipoprotein nanoparticles (TLP). In vitro , TLPs loaded with a CD95L derived siRNA (siL3) selectively silenced a biosensor comprised of Venus and CD95L ORF and killed ovarian cancer cells. In vivo , two siRNA-TLPs (siL2-TLP and siL3-TLP) reduced tumor growth similarly as observed for cells expressing the shL3 vector. These data suggest that it is possible to kill ovarian cancer cells in vivo via DISE induction using siRNA-TLPs., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts to disclose.
- Published
- 2017
- Full Text
- View/download PDF
39. Global developmental delay and intellectual disability associated with a de novo TOP2B mutation.
- Author
-
Lam CW, Yeung WL, and Law CY
- Subjects
- Adolescent, Female, Humans, Exome Sequencing, DNA Topoisomerases, Type II genetics, Developmental Disabilities complications, Developmental Disabilities genetics, Intellectual Disability complications, Mutation
- Abstract
Background: More than 100 genes had been identified for autism spectrum disorder (ASD). With the advancement of whole-exome/genome sequencing (WES/WGS), disease-causing gene in ASD can be identified in a holistic and unbiased approach. The identification of new ASD genes can further explore the molecular basis of ASD., Methods: We report a 15yo girl with developmental delay, intellectual disability, hypotonia, microcephaly and autistic feature. She first presented at 6months old with primitive response to noise. Physical examination showed the patient was hypotonic despite normal muscle power and reflexes. She also had progressive microcephaly. Developmental assessment at 6y showed the patient had a corresponding functional age of 1y. The patient also had autistic feature., Results: The patient had no abnormal biochemical or radiological findings. To investigate the molecular basis of the clinical presentation, we applied clinical whole-exome sequencing (WES) for the proband and the family, and we identified a novel de novo heterozygous missense pathogenic variant, TOP2B: NM_001068.2:c.172C>T; NP_001059.2:p.His58Tyr. TOP2B encodes for the enzyme, topoisomerase II isoenzyme beta which is abundant in both developing and adult brain. Defect of topoisomerase is also known to cause ASD., Conclusions: Using clinical WES, we were able to identify the disease-causing gene for this patient in a holistic approach and end the diagnostic odyssey with a therapeutic impact., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
40. Novel presenilin 1 mutation (p.F386I) in a Chinese family with early-onset Alzheimer's disease.
- Author
-
Shea YF, Chan AO, Chu LW, Lee SC, Law CY, See CH, Yiu KL, and Chiu PK
- Subjects
- Adult, Aged, Asian People genetics, Codon genetics, Female, Genes, Dominant genetics, Heterozygote, Humans, Isoleucine genetics, Male, Middle Aged, Phenylalanine genetics, Alzheimer Disease genetics, Genetic Association Studies, Mutation, Missense genetics, Presenilin-1 genetics
- Abstract
Autosomal dominant familial Alzheimer's disease accounts for 0.5% of all Alzheimer's disease. A familial Alzheimer's disease Chinese family, with 7 affected family members, underwent PSEN1 screening in 3 affected family members. A heterozygous novel missense mutation in the PSEN1 gene c.1156T>A, altering phenylalanine to isoleucine at codon 386, was identified. Because the change occurred in conserved domains of this gene and cosegregated with affected family members, this change may have a mutagenic and probably pathogenic effect., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
41. Limb girdle myasthenia with digenic RAPSN and a novel disease gene AK9 mutations.
- Author
-
Lam CW, Wong KS, Leung HW, and Law CY
- Subjects
- 5' Untranslated Regions, Adenylate Kinase metabolism, Adult, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 6 genetics, Exome, Female, Homozygote, Humans, Male, Myasthenic Syndromes, Congenital diagnosis, Pedigree, Polymorphism, Single Nucleotide, Adenylate Kinase genetics, Genes, Modifier, Mutation, Myasthenic Syndromes, Congenital genetics
- Abstract
Though dysfunction of neuromuscular junction (NMJ) is associated with congenital myasthenic syndrome (CMS), the proteins involved in neuromuscular transmission have not been completely identified. In this study, we aimed to identify a novel CMS gene in a consanguineous family with limb-girdle type CMS. Homozygosity mapping of the novel CMS gene was performed using high-density single-nucleotide polymorphism microarrays. The variants in CMS gene were identified by whole-exome sequencing (WES) and Sanger sequencing. A 20 MB-region of homozygosity (ROH) was mapped on chromosome 6q15-21. This was the only ROH that present in all clinically affected siblings and absent in all clinically unaffected siblings. WES showed a novel variant of AK9 gene located in this ROH. This variant was a start-gain mutation and introduced a cryptic 5'-UTR signal in intron 5 of the AK9 gene. The normal splicing signal would be interfered by the cryptic translation signal leading to defective splicing. Another 25 MB-ROH was found on chromosome 11p13-q12 in all siblings. WES showed a homozygous RAPSN pathogenic variant in this ROH. Since RAPSN-associated limb-girdle type CMS was only manifested in AK9 homozygous variant carriers, the disease phenotype was of digenic inheritance, and was determined by the novel disease modifier AK9 which provides NTPs for N-glycosylation. This is the first time that this specific genotype-phenotype correlation is reported. Importantly, the AK9-associated nucleotide deficiency may replete by dietary supplements. Since AK9 is a disease modifier, enhancing N-glycosylation by increasing dietary nucleotides may be a new therapeutic option for CMS patients.
- Published
- 2017
- Full Text
- View/download PDF
42. A common PRRT2 mutation in familial paroxysmal kinesigenic dyskinesia in Hong Kong: a case series of 16 patients.
- Author
-
Law CY, Yeung WL, Cheung YF, Chan HF, Fung E, Hui J, Yung IO, Yuen YP, Chan AO, and Lam CW
- Subjects
- Adolescent, Adult, Family Health, Female, Hong Kong, Humans, Male, Middle Aged, Mutation, Young Adult, Dystonia genetics, Membrane Proteins genetics, Nerve Tissue Proteins genetics
- Published
- 2016
- Full Text
- View/download PDF
43. Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia.
- Author
-
To KK, Lee KC, Wong SS, Sze KH, Ke YH, Lui YM, Tang BS, Li IW, Lau SK, Hung IF, Law CY, Lam CW, and Yuen KY
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Early Diagnosis, Female, Humans, Male, Middle Aged, Plasma chemistry, Prognosis, Young Adult, Biomarkers blood, Community-Acquired Infections diagnosis, Community-Acquired Infections pathology, Lipids blood, Pneumonia diagnosis, Pneumonia pathology
- Abstract
Early diagnosis of acute community-acquired pneumonia (CAP) is important in patient triage and treatment decisions. To identify biomarkers that distinguish patients with CAP from non-CAP controls, we conducted an untargeted global metabolome analysis for plasma samples from 142 patients with CAP (CAP cases) and 97 without CAP (non-CAP controls). Thirteen lipid metabolites could discriminate between CAP cases and non-CAP controls with area-under-the-receiver-operating-characteristic curve of >0.8 (P ≤ 10(-9)). The levels of glycosphingolipids, sphingomyelins, lysophosphatidylcholines and L-palmitoylcarnitine were higher, while the levels of lysophosphatidylethanolamines were lower in the CAP cases than those in non-CAP controls. All 13 metabolites could distinguish CAP cases from the non-infection, extrapulmonary infection and non-CAP respiratory tract infection subgroups. The levels of trihexosylceramide (d18:1/16:0) were higher, while the levels of lysophosphatidylethanolamines were lower, in the fatal than those of non-fatal CAP cases. Our findings suggest that lipid metabolites are potential diagnostic and prognostic biomarkers for CAP., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
44. Novel large deletion in AVPR2 gene causing copy number variation in a patient with X-linked nephrogenic diabetes insipidus.
- Author
-
Cho SY, Law CY, Ng KL, and Lam CW
- Subjects
- Humans, Infant, Male, Mutation, Polymerase Chain Reaction, DNA Copy Number Variations, Diabetes Insipidus, Nephrogenic genetics, Gene Deletion, Genetic Diseases, X-Linked, Genetic Linkage, Receptors, Vasopressin genetics
- Abstract
Background: The diagnosis of cranial and nephrogenic diabetes insipidus (DI) can be clinically challenging. The application of molecular genetic analysis can help in resolving diagnostic difficulties., Case: A 3 month-old boy presented with recurrent polyuria was admitted to Intensive Care Unit and was treated as DI. The patient also had a strong family history of polyuria affecting his maternal uncles. Molecular genetic analysis using Single Nucleotide Polymorphism (SNP) array detected a large deletion located at Xq28 region and the breakpoint was identified using PCR and Sanger sequencing. An 11,535 bp novel deletion affecting the entire APVR2 gene and the last intron and exon of the ARHGAP4 gene was confirmed. This large deletion is likely due to the 7-bp microhomology sequence at the junctions of both 5' and 3' breakpoints. No disease-causing mutation was identified for AQP2., Conclusion: We report a novel deletion in a Chinese patient with congenital nephrogenic DI. We suggested that patients with suspected congenital DI should undergo genetic analysis of AVPR2 and AQP2 genes. A definitive diagnosis can benefit patient by treatment of hydrochlorothiazide and amiloride and avoiding unnecessary investigations., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
45. Lysosomal membrane permeabilization is involved in oxidative stress-induced apoptotic cell death in LAMP2-deficient iPSCs-derived cerebral cortical neurons.
- Author
-
Law CY, Siu CW, Fan K, Lai WH, Au KW, Lau YM, Wong LY, Ho JCY, Lee YK, Tse HF, and Ng KM
- Abstract
Patients with Danon disease may suffer from severe cardiomyopathy, skeletal muscle dysfunction as well as varying degrees of mental retardation, in which the primary deficiency of lysosomal membrane-associated protein-2 (LAMP2) is considerably associated. Owing to the scarcity of human neurons, the pathological role of LAMP2 deficiency in neural injury of humans remains largely elusive. However, the application of induced pluripotent stem cells (iPSCs) may shed light on overcoming such scarcity. In this study, we obtained iPSCs derived from a patient carrying a mutated LAMP2 gene that is associated with Danon disease. By differentiating such LAMP2-deficient iPSCs into cerebral cortical neurons and with the aid of various biochemical assays, we demonstrated that the LAMP2-deficient neurons are more susceptible to mild oxidative stress-induced injury. The data from MTT assay and apoptotic analysis demonstrated that there was no notable difference in cellular viability between the normal and LAMP2-deficient neurons under non-stressed condition. When exposed to mild oxidative stress (10 μM H
2 O2 ), the LAMP2-deficient neurons exhibited a significant increase in apoptosis. Surprisingly, we did not observe any aberrant accumulation of autophagic materials in the LAMP2-deficient neurons under such stress condition. Our results from cellular fractionation and inhibitor blockade experiments further revealed that oxidative stress-induced apoptosis in the LAMP2-deficient cortical neurons was caused by increased abundance of cytosolic cathepsin L. These results suggest the involvement of lysosomal membrane permeabilization in the LAMP2 deficiency associated neural injury.- Published
- 2016
- Full Text
- View/download PDF
46. Clinical whole-exome sequencing reveals a novel missense pathogenic variant of GNAO1 in a patient with infantile-onset epilepsy.
- Author
-
Law CY, Chang ST, Cho SY, Yau EK, Ng GS, Fong NC, and Lam CW
- Subjects
- Age of Onset, Female, Humans, Infant, Epilepsy genetics, Exome genetics, GTP-Binding Protein alpha Subunits, Gi-Go genetics, Mutation, Missense genetics, Sequence Analysis, DNA
- Abstract
Background: The cause of infantile-onset epilepsy is complex and is not easily recognized clinically, particularly in paediatric patients who present with non-specific neurological signs, no radiological abnormalities and no metabolic changes., Case: We report a case of infantile-onset epilepsy in a 10-month-old Chinese girl who presented with non-specific neurological signs, no radiological abnormalities and no biochemical disturbances. She first presented at birth with twitching movements and convulsions of an unknown aetiology. Ambulatory EEG showed epileptic rhythmic activities, the presence of asynchrony and runs of sharp waves over the right parietal and central areas. Given the non-specific neurological features and negative structural and biochemical findings, we applied clinical whole-exome sequencing (WES) to determine the underlying aetiology. WES revealed a novel heterozygous missense pathogenic variant, GNAO1:NM_020988.2:c.118G>A; NP_066268.1:p.Gly40Arg. A genetic analysis of the family confirmed the variant identified is a de novo mutation., Conclusions: Clinical WES can streamline genetic analysis and sort out pathogenic genes in an unbiased approach. GNAO1 is a disease-causing gene for the autosomal dominant form of early infantile epileptic encephalopathy. The novel pathogenic variant identified in this case should contribute to our understanding of the expanding spectrum of infantile-onset epilepsy., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
47. Novel POLG mutation in a patient with sensory ataxia, neuropathy, ophthalmoparesis and stroke.
- Author
-
Lam CW, Law CY, Siu WK, Fung CW, Yau MM, Huen KF, Lee HH, and Mak CM
- Subjects
- Adolescent, DNA Polymerase gamma, Female, Humans, Ophthalmoplegia complications, Ataxia complications, Ataxia genetics, DNA-Directed DNA Polymerase genetics, Mutation genetics, Ophthalmoplegia genetics, Polyneuropathies complications, Polyneuropathies genetics, Stroke complications, Stroke genetics
- Abstract
Background: Clinical diagnosis of POLG-related disorders can be challenging because the phenotypic spectrums are heterogeneous which can mimic different types of mitochondrial disorders., Case: We report a case of POLG-related disorder in an 18y Chinese girl who had been diagnosed as MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) for the past 8y. She first presented at 10y with sudden onset of headache, repeated focal seizures and visual loss, complicated with residual sensory and motor neuropathy, ophthalmoparesis and cortical blindness. MRI brain showed extensive cytotoxic edema and ischemia in bilateral parietal-occipital lobes. Mutation analysis for common point mutations in the mitochondrial DNA and muscle biopsy was negative. She was referred to us for mitochondrial whole genome analysis. However, no pathogenic variants can be determined. We initiated further genetic analysis for POLG which confirmed compound heterozygous mutations NM_002693.2:c.925C>T (p.Arg309Cys) and a novel mutation c.2244G>T (p.Trp748Cys). Both were determined to be pathogenic using in silico analysis., Conclusions: The novel mutation contributes to the expanding spectrum of disease-causing mutations. A definitive diagnosis can benefit our patient and also the relatives by avoiding sodium valproate induced liver toxicity in POLG patients and also the heterozygotes., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
48. Lipid mediators of inflammation as novel plasma biomarkers to identify patients with bacteremia.
- Author
-
To KK, Lee KC, Wong SS, Lo KC, Lui YM, Jahan AS, Wu AL, Ke YH, Law CY, Sze KH, Lau SK, Woo PC, Lam CW, and Yuen KY
- Subjects
- Adult, Aged, Aged, 80 and over, Bacteremia blood, Biomarkers blood, Carnitine analogs & derivatives, Carnitine blood, Chromatography, High Pressure Liquid, Fatty Acids blood, Female, Humans, Male, Metabolomics, Middle Aged, Prognosis, ROC Curve, Sphingolipids blood, Bacteremia diagnosis, Inflammation Mediators isolation & purification, Lipids blood
- Abstract
Objectives: Rapid diagnostic tests for bacteremia are important for early treatment to improve clinical outcome. We sought to identify plasma biomarkers that can identify patients with bacteremia using an untargeted global metabolomic analysis., Methods: Plasma metabolomic profiles were analyzed for 145 adult patients with (cases) and without (controls) bacteremia using ultra-high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). All metabolites were compared between cases and controls using a 2-tier filtering approach, and each metabolite underwent receiver operating characteristic (ROC) curve analysis. Individual metabolites that distinguish between cases and controls were characterized. Subgroup analysis was performed to identify metabolites with prognostic significance., Results: After 2-tier filtering, 128 molecular features were identified to be potential biomarkers that could distinguish cases from controls. Five metabolites had an area under the ROC curve (AUC) of >0.8 in ROC curve analysis, including a sphingolipid, an acylcarnitine, a fatty acid ester, and 2 glycerophosphocholines. These metabolites could distinguish cases from controls in the unsupervised hierarchical clustering analysis. Subgroup analysis of bacteremic patients showed that the level of trans-2,3,4-trimethoxycinnamate was lower in fatal than non-fatal cases., Conclusions: Plasma lipid mediators of inflammation can distinguish bacteremia cases from non-bacteremia controls. These biomarkers may be used as targets for rapid test in clinical practice., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
49. NMR-based urinalysis for rapid diagnosis of β-ureidopropionase deficiency in a patient with Dravet syndrome.
- Author
-
Lam CW, Law CY, Leung KF, Lai CK, Pak-lam Chen S, Chan B, Chan KY, Yuen YP, Mak CM, and Yan-wo Chan A
- Subjects
- Amidohydrolases genetics, Amidohydrolases urine, Epilepsies, Myoclonic complications, Gas Chromatography-Mass Spectrometry methods, Homozygote, Humans, Infant, Male, NAV1.1 Voltage-Gated Sodium Channel genetics, Urea analogs & derivatives, Urea urine, beta-Alanine analogs & derivatives, beta-Alanine urine, Abnormalities, Multiple urine, Amidohydrolases deficiency, Brain Diseases urine, Epilepsies, Myoclonic genetics, Epilepsies, Myoclonic urine, Magnetic Resonance Spectroscopy methods, Movement Disorders urine, Purine-Pyrimidine Metabolism, Inborn Errors urine, Urinalysis methods
- Abstract
Background: Beta-ureidopropionase deficiency is a rare inborn error of metabolism (IEM) affecting pyrimidine metabolism. To-date, about 30 genetically confirmed cases had been reported. The clinical phenotypes of this condition are variable; some patients were asymptomatic while some may present with developmental delay or autistic features. In severe cases, patients may present with profound neurological deficit including hypotonia, seizures and mental retardation. Using NMR-based urinalysis, this condition can be rapidly diagnosed within 15 min., Case: An 11-month-old Chinese boy had dual molecular diagnoses, β-ureidopropionase deficiency and Dravet syndrome. He presented with intractable and recurrent convulsions, global developmental delay and microcephaly. Urine organic acid analysis using GC-MS and NMR-based urinalysis showed excessive amount of β-ureidopropionic acid and β-ureidoisobutyric acid, the two disease-specific markers for β-ureidopropionase deficiency. Genetic analysis confirmed homozygous known disease-causing mutation UPB1 NM_016327.2: c.977G>A; NP_057411.1:p.R326Q. In addition, genetic analysis for Dravet syndrome showed the presence of heterozygous disease-causing mutation SCN1A NM_001165963.1:c.4494delC; NP_001159435.1:p.F1499Lfs*2., Conclusions: The differentiation between Dravet syndrome and β-ureidopropionase deficiency is clinically challenging since both conditions share overlapping clinical features. The detection of urine β-ureidoisobutyric and β-ureidopropionic acids using NMR or GC-MS is helpful in laboratory diagnosis of β-ureidopropionase deficiency. The disease-causing mutation, c.977G>A of β-ureidopropionase deficiency, is highly prevalent in Chinese population (allele frequency=1.7%); β-ureidopropionase deficiency screening test should be performed for any patients with unexplained neurological deficit, developmental delay or autism., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
50. NMR-based urinalysis for beta-ketothiolase deficiency.
- Author
-
Law CY, Lam CW, Ching CK, Yau KC, Ho TW, Lai CK, and Mak CM
- Subjects
- Acetyl-CoA C-Acyltransferase urine, Butanones urine, Gas Chromatography-Mass Spectrometry, Glycine analogs & derivatives, Glycine urine, Humans, Infant, Ketones urine, Male, Acetyl-CoA C-Acyltransferase deficiency, Amino Acid Metabolism, Inborn Errors diagnosis, Amino Acid Metabolism, Inborn Errors urine, Biomarkers urine, Magnetic Resonance Imaging methods, Urinalysis methods
- Abstract
Background: Beta-ketothiolase deficiency is a rare inborn errors of metabolism (IEM) affecting the catabolism of isoleucine, characterized by severe ketoacidosis in children of 6 to 24months old. A prompt diagnosis is of paramount importance as the metabolic decompensation can be effectively reverted by glucose infusion and health outcomes are improved on a protein-restricted diet. Currently, majority of the laboratory diagnosis were made based on mass-spectrometry and molecular genetics while little is mentioned on the advancement of nuclear magnetic resonance (NMR) spectroscopy for the diagnosis of this condition., Case: We report a case of beta-ketothiolase deficiency in a 1-y-old Chinese boy who presented with repeated vomiting, impaired consciousness and severe ketoacidosis. NMR urinalysis detected excessive amount of butanone (a disease specific marker of beta-ketothiolase deficiency), tiglylglycine, (intermediate of isoleucine catabolism) and ketones. Diagnosis of beta-ketothiolase deficiency was further established by molecular genetic studies of ACAT1 gene of the proband., Conclusions: This case illustrated that NMR-based urinalysis is complementary to organic acid analysis for diagnosis of beta-ketothiolase deficiency. The operation of NMR is simple and fast; sample preparation is a two-step procedure while the NMR acquisition is automatic and usually takes <15min. We envisage that NMR analysis will become more available in clinical laboratories and will play an important role in acute pediatric care., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.