164 results on '"Florijn, Ralph J."'
Search Results
2. Clinical, Genetic, and Histopathological Characteristics of CRX-associated Retinal Dystrophies
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Hahn, Leo C., van der Veen, Isa, Georgiou, Michalis, van Schooneveld, Mary J., ten Brink, Jacoline B., Florijn, Ralph J., Mahroo, Omar A., de Carvalho, Emanuel R., Webster, Andrew R., Bergen, Arthur A., Michaelides, Michel, and Boon, Camiel J.F.
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- 2024
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3. Utilization of automated cilia analysis to characterize novel INPP5E variants in patients with non-syndromic retinitis pigmentosa
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Whiting, Kae R., primary, Haer-Wigman, Lonneke, additional, Florijn, Ralph J., additional, van Beek, Ronald, additional, Oud, Machteld M., additional, Plomp, Astrid S., additional, Boon, Camiel J. F., additional, Kroes, Hester Y., additional, and Roepman, Ronald, additional
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- 2024
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4. GNB1 and obesity: Evidence for a correlation between haploinsufficiency and syndromic obesity
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Kleinendorst, Lotte, primary, Abawi, Ozair, additional, Vos, Niels, additional, van der Valk, Eline S., additional, Maas, Saskia M., additional, Morgan, Angela T., additional, Hildebrand, Michael S., additional, Da Silva, Jorge D., additional, Florijn, Ralph J., additional, Lauffer, Peter, additional, Visser, Jenny A., additional, van Rossum, Elisabeth F. C., additional, van den Akker, Erica L. T., additional, and van Haelst, Mieke M., additional
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- 2024
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5. Genotype-phenotype correlation in pseudoxanthoma elasticum
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Bartstra, Jonas W., Risseeuw, Sara, de Jong, Pim A., van Os, Bram, Kalsbeek, Lianne, Mol, Chris, Baas, Annette F., Verschuere, Shana, Vanakker, Olivier, Florijn, Ralph J., Hendrikse, Jeroen, Mali, Willem, Imhof, Saskia, Ossewaarde-van Norel, Jeannette, van Leeuwen, Redmer, and Spiering, Wilko
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- 2021
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6. GNB1 and obesity:Evidence for a correlation between haploinsufficiency and syndromic obesity
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Kleinendorst, Lotte, Abawi, Ozair, Vos, Niels, van der Valk, Eline S., Maas, Saskia M., Morgan, Angela T., Hildebrand, Michael S., Da Silva, Jorge D., Florijn, Ralph J., Lauffer, Peter, Visser, Jenny A., van Rossum, Elisabeth F.C., van den Akker, Erica L.T., van Haelst, Mieke M., Kleinendorst, Lotte, Abawi, Ozair, Vos, Niels, van der Valk, Eline S., Maas, Saskia M., Morgan, Angela T., Hildebrand, Michael S., Da Silva, Jorge D., Florijn, Ralph J., Lauffer, Peter, Visser, Jenny A., van Rossum, Elisabeth F.C., van den Akker, Erica L.T., and van Haelst, Mieke M.
- Abstract
Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader–Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication.
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- 2024
7. Clinical, Genetic and Histopathological Characteristics of CRX-associated Retinal Dystrophies
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Hahn, Leo C, van der Veen, Isa, Georgiou, Michalis, van Schooneveld, Mary J, Ten Brink, Jacoline B, Florijn, Ralph J, Mahroo, Omar A, de Carvalho, Emanuel R, Webster, Andrew R, Bergen, Arthur A, Michaelides, Michel, Boon, Camiel J F, Hahn, Leo C, van der Veen, Isa, Georgiou, Michalis, van Schooneveld, Mary J, Ten Brink, Jacoline B, Florijn, Ralph J, Mahroo, Omar A, de Carvalho, Emanuel R, Webster, Andrew R, Bergen, Arthur A, Michaelides, Michel, and Boon, Camiel J F
- Abstract
PURPOSE: To describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRX gene (CRX-RDs).DESIGN: Retrospective multicenter cohort study including histopathology.SUBJECTS: Thirty-nine patients from 31 families with pathogenic variants in the CRX gene.METHODS: Clinical data of 152 visits were collected from medical records with a median follow-up time of 9.1 years (IQR, 3.3-15.3 years; range, 0.0-48.8 years). Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset CRX-RD was performed.MAIN OUTCOME MEASURES: Visual acuity, retinal imaging, electroretinography (ERG), genotype-phenotype correlation, and histopathological examination were evaluated.RESULTS: The age at onset ranged from birth to the 8th decade of life. Median visual acuity was 1.00 logMAR (IQR, 0.69-1.48 logMAR; range, 0.06-3.00 logMAR) at a mean age of 52.0 ± 19.9 years (range, 4.6-81.9 years). Sufficient imaging was available for 36 out of 39 patients (92.3%), and all showed degeneration of at least the macula. Out of these 36 patients, 22 (61.1%) had only macular dystrophy. Another 10 patients (27.8%) had additional degeneration beyond the vascular arcades, and 4 patients (11.1%) panretinal degeneration. Two patients (5.1%) had Leber congenital amaurosis (LCA). In total, 21 different disease-associated heterozygous CRX variants were identified (10 missense, 8 frameshift, 2 deletion, 1 deletion-insertion variants). Missense variants in the CRX homeodomain and two variants deleting all functional domains, thus causing haploinsufficiency, generally tended to cause milder late-onset phenotypes. Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset retinal dystrophy due to a heterozygous deletion of exons 3 and 4 of the CRX gene revealed loss of laminar integrity and widespread photoreceptor degeneration especially in the central retina, with ex
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- 2024
8. Efficacy of Carbonic Anhydrase Inhibitors on Cystoid Fluid Collections and Visual Acuity in Patients with X-Linked Retinoschisis
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Hensman, Jonathan, primary, Hahn, Leo C., additional, van Schooneveld, Mary J., additional, Diederen, Roselie M.H., additional, ten Brink, Jacoline B., additional, Florijn, Ralph J., additional, Bergen, Arthur A., additional, Strubbe, Ine, additional, Heutinck, Pam, additional, van Genderen, Maria M., additional, van den Born, L. Ingeborgh, additional, Thiadens, Alberta A., additional, de Zaeytijd, Julie, additional, Leroy, Bart P., additional, Hoyng, Carel B., additional, and Boon, Camiel J.F., additional
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- 2023
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9. CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF RHO-ASSOCIATED RETINITIS PIGMENTOSA: A Long-Term Follow-Up Study
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Nguyen, Xuan-Thanh-An, Talib, Mays, van Cauwenbergh, Caroline, van Schooneveld, Mary J., Fiocco, Marta, Wijnholds, Jan, ten Brink, Jacoline B., Florijn, Ralph J., Schalij-Delfos, Nicoline E., Dagnelie, Gislin, van Genderen, Maria M., de Baere, Elfride, Meester-Smoor, Magda A., De Zaeytijd, Julie, Balikova, Irina, Thiadens, Alberta A., Hoyng, Carel B., Klaver, Caroline C., van den Born, L. Ingeborgh, Bergen, Arthur A., Leroy, Bart P., and Boon, Camiel J.F.
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- 2021
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10. Utilization of automated cilia analysis to characterize novel INPP5Evariants in patients with non-syndromic retinitis pigmentosa
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Whiting, Kae R., Haer-Wigman, Lonneke, Florijn, Ralph J., van Beek, Ronald, Oud, Machteld M., Plomp, Astrid S., Boon, Camiel J. F., Kroes, Hester Y., and Roepman, Ronald
- Abstract
INPP5Eencodes inositol polyphosphate-5-phosphatase E, an enzyme involved in regulating the phosphatidylinositol (PIP) makeup of the primary cilium membrane. Pathogenic variants in INPP5Ehence cause a variety of ciliopathies: genetic disorders caused by dysfunctional cilia. While the majority of these disorders are syndromic, such as the neuronal ciliopathy Joubert syndrome, in some cases patients will present with an isolated phenotype—most commonly non-syndromic retinitis pigmentosa (RP). Here, we report two novel variants in INPP5Eidentified in two patients with non-syndromic RP: patient 1 with compound heterozygous variants (c.1516C > T, p.(Q506*), and c.847G > A, p.(A283T)) and patient 2 with a homozygous variant (c.1073C > T, p.(P358L)). To determine whether these variants were causative for the phenotype in the patients, automated ciliary phenotyping of patient-derived dermal fibroblasts was performed for percent ciliation, cilium length, retrograde IFT trafficking, and INPP5E localization. In both patients, a decrease in ciliary length and loss of INPP5E localization in the primary cilia were seen. With these molecular findings, we can confirm functionally that the novel variants in INPP5Eare causative for the RP phenotypes seen in both patients. Additionally, this study demonstrates the usefulness of utilizing ciliary phenotyping as an assistant in ciliopathy diagnosis and phenotyping.
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- 2024
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11. CLINICAL AND GENETIC CHARACTERISTICS OF MALE PATIENTS WITH RPGR-ASSOCIATED RETINAL DYSTROPHIES: A Long-Term Follow-up Study
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Talib, Mays, van Schooneveld, Mary J., Thiadens, Alberta A., Fiocco, Marta, Wijnholds, Jan, Florijn, Ralph J., Schalij-Delfos, Nicoline E., van Genderen, Maria M., Putter, Hein, Cremers, Frans P. M., Dagnelie, Gislin, ten Brink, Jacoline B., Klaver, Caroline C. W., van den Born, L. Ingeborgh, Hoyng, Carel B., Bergen, Arthur A., and Boon, Camiel J. F.
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- 2019
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12. LONG-TERM FOLLOW-UP OF PATIENTS WITH CHOROIDEREMIA WITH SCLERAL PITS AND TUNNELS AS A NOVEL OBSERVATION
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van Schuppen, Sanne M., Talib, Mays, Bergen, Arthur A., ten Brink, Jacoline B., Florijn, Ralph J., Boon, Camiel J. F., and van Schooneveld, Mary J.
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- 2018
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13. The Natural History of Leber Congenital Amaurosis and Cone–Rod Dystrophy Associated with Variants in the GUCY2D Gene
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Hahn, Leo C., primary, Georgiou, Michalis, additional, Almushattat, Hind, additional, van Schooneveld, Mary J., additional, de Carvalho, Emanuel R., additional, Wesseling, Nieneke L., additional, ten Brink, Jacoline B., additional, Florijn, Ralph J., additional, Lissenberg-Witte, Birgit I., additional, Strubbe, Ine, additional, van Cauwenbergh, Caroline, additional, de Zaeytijd, Julie, additional, Walraedt, Sophie, additional, de Baere, Elfride, additional, Mukherjee, Rajarshi, additional, McKibbin, Martin, additional, Meester-Smoor, Magda A., additional, Thiadens, Alberta A.H.J., additional, Al-Khuzaei, Saoud, additional, Akyol, Engin, additional, Lotery, Andrew J., additional, van Genderen, Maria M., additional, Ossewaarde-van Norel, Jeannette, additional, van den Born, L. Ingeborgh, additional, Hoyng, Carel B., additional, Klaver, Caroline C.W., additional, Downes, Susan M., additional, Bergen, Arthur A., additional, Leroy, Bart P., additional, Michaelides, Michel, additional, and Boon, Camiel J.F., additional
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- 2022
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14. X-Linked Retinoschisis Novel Clinical Observations and Genetic Spectrum in 340 Patients
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Hahn, L.C., Schooneveld, M.J. van, Wesseling, N.L., Florijn, Ralph J., Brink, Jacoline B. ten, Lissenberg-Witte, Birgit I., Klaver, C.C.W., Hoyng, C.B., Bergen, A.A., Boon, C.J.F., Hahn, L.C., Schooneveld, M.J. van, Wesseling, N.L., Florijn, Ralph J., Brink, Jacoline B. ten, Lissenberg-Witte, Birgit I., Klaver, C.C.W., Hoyng, C.B., Bergen, A.A., and Boon, C.J.F.
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- 2022
15. The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences
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Kruijt, Charlotte C, Gradstein, Libe, Bergen, Arthur A, Florijn, Ralph J, Arveiler, Benoit, Lasseaux, Eulalie, Zanlonghi, Xavier, Bagdonaite-Bejarano, Laura, Fulton, Anne B, Yahalom, Claudia, Blumenfeld, Anat, Perez, Yonatan, Birk, Ohad S, de Wit, Gerard C, Schalij-Delfos, Nicoline E, van Genderen, Maria M, Kruijt, Charlotte C, Gradstein, Libe, Bergen, Arthur A, Florijn, Ralph J, Arveiler, Benoit, Lasseaux, Eulalie, Zanlonghi, Xavier, Bagdonaite-Bejarano, Laura, Fulton, Anne B, Yahalom, Claudia, Blumenfeld, Anat, Perez, Yonatan, Birk, Ohad S, de Wit, Gerard C, Schalij-Delfos, Nicoline E, and van Genderen, Maria M
- Abstract
Purpose: The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to describe the phenotypic spectrum, and to compare it to albinism.Subjects and Methods: We retrospectively collected molecular, ophthalmic, and electrophysiological data of 28 patients molecularly confirmed with FHONDA from the Netherlands (9), Israel (13), France (2), and the United States of America (4). We compared the data to that of 133 Dutch patients with the 3 most common types of albinism in the Netherlands: oculocutaneous albinism type 1 (49), type 2 (41), and ocular albinism (43).Results: Patients with FHONDA had a total of 15 different mutations in SLC38A8, of which 6 were novel. Excluding missing data, all patients had moderate to severe visual impairment (median visual acuity [VA] = 0.7 logMAR, interquartile range [IQR] = 0.6-0.8), nystagmus (28/28), and grade 4 foveal hypoplasia (17/17). Misrouting was present in all nine tested patients. None of the patients had any signs of hypopigmentation of skin and hair. VA in albinism was better (median = 0.5 logMAR, IQR = 0.3-0.7, P 0.006) and the phenotypes were more variable: 14 of 132 without nystagmus, foveal hypoplasia grades 1 to 4, and misrouting absent in 16 of 74.Conclusions: Compared to albinism, the FHONDA syndrome appears to have a more narrow phenotypic spectrum, consisting of nonprogressive moderately to severely reduced VA, nystagmus, severe foveal hypoplasia, and misrouting. The co-occurrence of nystagmus, foveal hypoplasia, and misrouting in the absence of hypopigmentation implies that these abnormalities are not caused by lack of melanin, which has important implications for understanding the pathogenesis of these features.
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- 2022
16. CRB1-associated retinal dystrophies: a prospective natural history study in anticipation of future clinical trials
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Nguyen, Xuan-Thanh-An, Talib, Mays, van Schooneveld, Mary J, Wijnholds, Jan, van Genderen, Maria M, Schalij-Delfos, Nicoline E, Klaver, Caroline C W, Talsma, Herman E, Fiocco, Marta, Florijn, Ralph J, Ten Brink, Jacoline B, Cremers, Frans P M, Meester-Smoor, Magda A, Ingeborgh van den Born, L, Hoyng, Carel B, Thiadens, Alberta A H J, Bergen, Arthur A, Boon, Camiel J F, Nguyen, Xuan-Thanh-An, Talib, Mays, van Schooneveld, Mary J, Wijnholds, Jan, van Genderen, Maria M, Schalij-Delfos, Nicoline E, Klaver, Caroline C W, Talsma, Herman E, Fiocco, Marta, Florijn, Ralph J, Ten Brink, Jacoline B, Cremers, Frans P M, Meester-Smoor, Magda A, Ingeborgh van den Born, L, Hoyng, Carel B, Thiadens, Alberta A H J, Bergen, Arthur A, and Boon, Camiel J F
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PURPOSE: To describe the natural disease course of CRB1-associated retinal dystrophies, and to identify clinical endpoints for future clinical trials.DESIGN: Single center, prospective case series.METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using ETDRS charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography (ERG), full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography and fundus autofluorescence imaging.RESULTS: Based on genetic, clinical and electrophysiological data, patients were diagnosed with retinitis pigmentosa (n = 19; 86%), cone-rod dystrophy (n = 2; 9%) or isolated macular dystrophy (n = 1; 5%). Two-year analysis of the entire cohort showed no significant changes in BCVA (p = 0.069) or V4e isopter seeing retinal areas (p = 0.616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at 2-year follow-up (p < 0.001). FST responses were measurable in patients with non-recordable ERGs. On average, FST responses remained stable during follow-up.CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up, and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical endpoint in future human treatment trials for CRB1-associated retinal dystrophies.
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- 2022
17. CRB1-Associated Retinal Dystrophies:A Prospective Natural History Study in Anticipation of Future Clinical Trials
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Nguyen, Xuan Thanh An, Talib, Mays, van Schooneveld, Mary J., Wijnholds, Jan, van Genderen, Maria M., Schalij-Delfos, Nicoline E., Klaver, Caroline C.W., Talsma, Herman E., Fiocco, Marta, Florijn, Ralph J., ten Brink, Jacoline B., Cremers, Frans P.M., Meester-Smoor, Magda A., van den Born, L. Ingeborgh, Hoyng, Carel B., Thiadens, Alberta A.H.J., Bergen, Arthur A., Boon, Camiel J.F., Nguyen, Xuan Thanh An, Talib, Mays, van Schooneveld, Mary J., Wijnholds, Jan, van Genderen, Maria M., Schalij-Delfos, Nicoline E., Klaver, Caroline C.W., Talsma, Herman E., Fiocco, Marta, Florijn, Ralph J., ten Brink, Jacoline B., Cremers, Frans P.M., Meester-Smoor, Magda A., van den Born, L. Ingeborgh, Hoyng, Carel B., Thiadens, Alberta A.H.J., Bergen, Arthur A., and Boon, Camiel J.F.
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PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials. DESIGN: Single-center, prospective case series. METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up. CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.
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- 2022
18. The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences
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Child Health, MS Oogheelkunde, Kruijt, Charlotte C., Gradstein, Libe, Bergen, Arthur A., Florijn, Ralph J., Arveiler, Benoit, Lasseaux, Eulalie, Zanlonghi, Xavier, Bagdonaite-Bejaran, Laura, Fulton, Anne B., Yahalom, Claudia, Blumenfeld, Anat, Perez, Yonatan, Birk, Ohad S., De Wit, Gerard C., Schalij-Delfos, Nicoline E., Van Genderen, Maria M., Child Health, MS Oogheelkunde, Kruijt, Charlotte C., Gradstein, Libe, Bergen, Arthur A., Florijn, Ralph J., Arveiler, Benoit, Lasseaux, Eulalie, Zanlonghi, Xavier, Bagdonaite-Bejaran, Laura, Fulton, Anne B., Yahalom, Claudia, Blumenfeld, Anat, Perez, Yonatan, Birk, Ohad S., De Wit, Gerard C., Schalij-Delfos, Nicoline E., and Van Genderen, Maria M.
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- 2022
19. X-Linked Retinoschisis: Novel Clinical Observations and Genetic Spectrum in 340 Patients
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Infection & Immunity, MS Oogheelkunde, Child Health, Hahn, Leo C., van Schooneveld, Mary J., Wesseling, Nieneke L., Florijn, Ralph J., ten Brink, Jacoline B., Lissenberg-Witte, Birgit I., Strubbe, Ine, Meester-Smoor, Magda A., Thiadens, Alberta A., Diederen, Roselie M., van Cauwenbergh, Caroline, de Zaeytijd, Julie, Walraedt, Sophie, de Baere, Elfride, Klaver, Caroline C.W., Ossewaarde-van Norel, Jeannette, Ingeborgh van den Born, L., Hoyng, Carel B., van Genderen, Maria M., Sieving, Paul A., Leroy, Bart P., Bergen, Arthur A., Boon, Camiel J.F., Infection & Immunity, MS Oogheelkunde, Child Health, Hahn, Leo C., van Schooneveld, Mary J., Wesseling, Nieneke L., Florijn, Ralph J., ten Brink, Jacoline B., Lissenberg-Witte, Birgit I., Strubbe, Ine, Meester-Smoor, Magda A., Thiadens, Alberta A., Diederen, Roselie M., van Cauwenbergh, Caroline, de Zaeytijd, Julie, Walraedt, Sophie, de Baere, Elfride, Klaver, Caroline C.W., Ossewaarde-van Norel, Jeannette, Ingeborgh van den Born, L., Hoyng, Carel B., van Genderen, Maria M., Sieving, Paul A., Leroy, Bart P., Bergen, Arthur A., and Boon, Camiel J.F.
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- 2022
20. CRB1-Associated Retinal Dystrophies: A Anticipation of Future Clinical Trials: A Prospective Natural History Study in Anticipation of Future Clinical Trials
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MS Oogheelkunde, Child Health, Nguyen, Xuan Thanh An, Talib, Mays, van Schooneveld, Mary J., Wijnholds, Jan, van Genderen, Maria M., Schalij-Delfos, Nicoline E., Klaver, Caroline C.W., Talsma, Herman E., Fiocco, Marta, Florijn, Ralph J., ten Brink, Jacoline B., Cremers, Frans P.M., Meester-Smoor, Magda A., van den Born, L. Ingeborgh, Hoyng, Carel B., Thiadens, Alberta A.H.J., Bergen, Arthur A., Boon, Camiel J.F., MS Oogheelkunde, Child Health, Nguyen, Xuan Thanh An, Talib, Mays, van Schooneveld, Mary J., Wijnholds, Jan, van Genderen, Maria M., Schalij-Delfos, Nicoline E., Klaver, Caroline C.W., Talsma, Herman E., Fiocco, Marta, Florijn, Ralph J., ten Brink, Jacoline B., Cremers, Frans P.M., Meester-Smoor, Magda A., van den Born, L. Ingeborgh, Hoyng, Carel B., Thiadens, Alberta A.H.J., Bergen, Arthur A., and Boon, Camiel J.F.
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- 2022
21. LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS: A Severe Phenotype With Considerable Interindividual Variability
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Mathijssen, Inge B., Florijn, Ralph J., van den Born, L. Ingeborgh, Zekveld-Vroon, Renate C., ten Brink, Jacoline B., Plomp, Astrid S., Baas, Frank, Meijers-Heijboer, Hanne, Bergen, Arthur A. B., and van Schooneveld, Mary J.
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- 2017
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22. X-Linked Retinoschisis
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Hahn, Leo C., primary, van Schooneveld, Mary J., additional, Wesseling, Nieneke L., additional, Florijn, Ralph J., additional, ten Brink, Jacoline B., additional, Lissenberg-Witte, Birgit I., additional, Strubbe, Ine, additional, Meester-Smoor, Magda A., additional, Thiadens, Alberta A., additional, Diederen, Roselie M., additional, van Cauwenbergh, Caroline, additional, de Zaeytijd, Julie, additional, Walraedt, Sophie, additional, de Baere, Elfride, additional, Klaver, Caroline C.W., additional, Ossewaarde-van Norel, Jeannette, additional, van den Born, L. Ingeborgh, additional, Hoyng, Carel B., additional, van Genderen, Maria M., additional, Sieving, Paul A., additional, Leroy, Bart P., additional, Bergen, Arthur A., additional, and Boon, Camiel J.F., additional
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- 2022
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23. CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials
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Nguyen, Xuan-Thanh-An, primary, Talib, Mays, additional, van Schooneveld, Mary J., additional, Wijnholds, Jan, additional, van Genderen, Maria M., additional, Schalij-Delfos, Nicoline E., additional, Klaver, Caroline C.W., additional, Talsma, Herman E., additional, Fiocco, Marta, additional, Florijn, Ralph J., additional, ten Brink, Jacoline B., additional, Cremers, Frans P.M., additional, Meester-Smoor, Magda A., additional, van den Born, L. Ingeborgh, additional, Hoyng, Carel B., additional, Thiadens, Alberta A.H.J., additional, Bergen, Arthur A., additional, and Boon, Camiel J.F., additional
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- 2022
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24. The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences
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Kruijt, Charlotte C., primary, Gradstein, Libe, additional, Bergen, Arthur A., additional, Florijn, Ralph J., additional, Arveiler, Benoit, additional, Lasseaux, Eulalie, additional, Zanlonghi, Xavier, additional, Bagdonaite-Bejarano, Laura, additional, Fulton, Anne B., additional, Yahalom, Claudia, additional, Blumenfeld, Anat, additional, Perez, Yonatan, additional, Birk, Ohad S., additional, de Wit, Gerard C., additional, Schalij-Delfos, Nicoline E., additional, and van Genderen, Maria M., additional
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- 2022
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25. The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in ABHD12: An Ophthalmic Perspective
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Nguyen, Xuan-Thanh-An, primary, Almushattat, Hind, additional, Strubbe, Ine, additional, Georgiou, Michalis, additional, Li, Catherina H. Z., additional, van Schooneveld, Mary J., additional, Joniau, Inge, additional, De Baere, Elfride, additional, Florijn, Ralph J., additional, Bergen, Arthur A., additional, Hoyng, Carel B., additional, Michaelides, Michel, additional, Leroy, Bart P., additional, and Boon, Camiel J. F., additional
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- 2021
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26. X-Linked Retinoschisis: Novel Clinical Observations and Genetic Spectrum in 340 Patients
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Hahn, Leo C., Schooneveld, Mary J. van, Wesseling, Nieneke L., Florijn, Ralph J., Brink, Jacoline B. ten, Lissenberg-Witte, Birgit I., Strubbe, Ine, Meester-Smoor, Magda A., Thiadens, Alberta A., Diederen, Roselie M., Van Cauwenbergh, Caroline, De Zaeytijd, Julie, WALRAEDT, SOPHIE, De Baere, Elfride, Klaver, Caroline C. W., Norel, Jeannette Ossewaarde-van, Born, L. Ingeborgh van den, Hoyng, Carel B., Genderen, Maria M. van, Sieving, Paul A., Leroy, Bart, Bergen, Arthur A., Boon, Camiel, Graduate School, Ophthalmology, Human Genetics, ANS - Complex Trait Genetics, ARD - Amsterdam Reproduction and Development, and Netherlands Institute for Neuroscience (NIN)
- Subjects
Adult ,Male ,Adolescent ,genetic structures ,Genotype ,JUVENILE RETINOSCHISIS ,Retinoschisis ,retinoschisis ,Visual Acuity ,Natural history ,Vision, Low ,CHILDREN ,PHENOTYPE ,MOUSE ,Blindness ,Surrogate end points ,Retina ,Medicine and Health Sciences ,VISUAL-ACUITY ,Electroretinography ,Humans ,CLINICAL FINDINGS ,Child ,Eye Proteins ,Genetic Association Studies ,Aged ,Retrospective Studies ,X-linked ,Aged, 80 and over ,MUTATIONS ,Optical Imaging ,GENE-THERAPY ,Infant ,NATURAL-HISTORY ,Middle Aged ,Retinal Photoreceptor Cell Outer Segment ,Ophthalmoscopy ,Phenotype ,Child, Preschool ,Female ,Tomography, Optical Coherence ,X-linked retinoschisis ,Follow-Up Studies - Abstract
Purpose: To describe the natural course, phenotype, and genotype of patients with X-linked retinoschisis (XLRS). Design: Retrospective cohort study. Participants: Three hundred forty patients with XLRS from 178 presumably unrelated families. Methods: This multicenter, retrospective cohort study reviewed medical records of patients with XLRS for medical history, symptoms, visual acuity (VA), ophthalmoscopy, full-field electroretinography, and retinal imaging (fundus photography, spectral-domain [SD] OCT, fundus autofluorescence). Main Outcome Measures: Age at onset, age at diagnosis, severity of visual impairment, annual visual decline, and electroretinography and imaging findings. Results: Three hundred forty patients were included with a mean follow-up time of 13.2 years (range, 0.1-50.1 years). The median ages to reach mild visual impairment and low vision were 12 and 25 years, respectively. Severe visual impairment and blindness were observed predominantly in patients older than 40 years, with a predicted prevalence of 35% and 25%, respectively, at 60 years of age. The VA increased slightly during the first 2 decades of life and subsequently transitioned into an average annual decline of 0.44% (P < 0.001). No significant difference was found in decline of VA between variants that were predicted to be severe and mild (P = 0.239). The integrity of the ellipsoid zone (EZ) as well as the photoreceptor outer segment (PROS) length in the fovea on SD OCT correlated significantly with VA (Spearman's rho = -0.759 [P < 0.001] and -0.592 [P = 0.012], respectively). Fifty-three different RS1 variants were found. The most common variants were the founder variant c.214G -> A (p.(G1u72Lys)) (101 patients [38.7%]) and a deletion of exon 3 (38 patients [14.6%]). Conclusions: Large variabilities in phenotype and natural course of XLRS were seen in this study. In most patients, XLRS showed a slow deterioration starting in the second decade of life, suggesting an optimal window of opportunity for treatment within the first 3 decades of life. The integrity of EZ as well as the PROS length on SD OCT may be important in choosing optimal candidates for treatment and as potential structural end points in future therapeutic studies. No clear genotype-phenotype correlation was found. (C) 2021 by the American Academy of Ophthalmology.
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- 2021
27. The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in ABHD12: An Ophthalmic Perspective
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Nguyen, Xuan-Thanh-An, Almushattat, Hind, Strubbe, Ine, Georgiou, Michalis, Li, Catherina H Z, van Schooneveld, Mary J, Joniau, Inge, De Baere, Elfride, Florijn, Ralph J, Bergen, Arthur A, Hoyng, Carel B, Michaelides, Michel, Leroy, Bart P, Boon, Camiel J F, Nguyen, Xuan-Thanh-An, Almushattat, Hind, Strubbe, Ine, Georgiou, Michalis, Li, Catherina H Z, van Schooneveld, Mary J, Joniau, Inge, De Baere, Elfride, Florijn, Ralph J, Bergen, Arthur A, Hoyng, Carel B, Michaelides, Michel, Leroy, Bart P, and Boon, Camiel J F
- Abstract
This study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the ABHD12 gene. A total of 15 patients from 12 different families were included, with a mean age of 36.7 years (standard deviation [SD] ± 11.0; range from 17.5 to 53.9) at the most recent examination. The presence and onset of neurological, audiological and ophthalmic symptoms were variable, with no evident order of symptom appearance. The mean best-corrected visual acuity was 1.1 logMAR (SD ± 0.9; range from 0.1 to 2.8; equivalent to 20/250 Snellen) and showed a trend of progressive decline. Different types of cataract were observed in 13 out of 15 patients (87%), which also included congenital forms of cataract. Fundus examination revealed macular involvement in all patients, ranging from alterations of the retinal pigment epithelium to macular atrophy. Intraretinal spicular hyperpigmentation was observed in 7 out of 15 patients (47%). From an ophthalmic perspective, clinical manifestations in patients with PHARC demonstrate variability with regard to their onset and severity. Given the variable nature of PHARC, an early multidisciplinary assessment is recommended to assess disease severity.
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- 2021
28. Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies
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Talib, Mays, van Schooneveld, Mary J, Wijnholds, Jan, van Genderen, Maria M, Schalij-Delfos, Nicoline E, Talsma, Herman E, Florijn, Ralph J, Ten Brink, Jacoline B, Cremers, Frans P M, Thiadens, Alberta A H J, van den Born, L Ingeborgh, Hoyng, Carel B, Meester-Smoor, Magda A, Bergen, Arthur A, Boon, Camiel J F, Talib, Mays, van Schooneveld, Mary J, Wijnholds, Jan, van Genderen, Maria M, Schalij-Delfos, Nicoline E, Talsma, Herman E, Florijn, Ralph J, Ten Brink, Jacoline B, Cremers, Frans P M, Thiadens, Alberta A H J, van den Born, L Ingeborgh, Hoyng, Carel B, Meester-Smoor, Magda A, Bergen, Arthur A, and Boon, Camiel J F
- Abstract
PURPOSE: To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints.METHODS: In this prospective cross-sectional study, 22 patients with genetically confirmed CRB1-RD (aged 6-74 years), and who had a decimal best-corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full-field electroretinography (ERG) and full-field stimulus testing (FST). Ten patients were from a genetic isolate (GI).RESULTS: Patients had retinitis pigmentosa (n = 19; GI and non-GI), cone-rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non-GI). Median age at first symptom onset was 3 years (range 0.8-49). Median decimal BCVA in the better and worse-seeing eye was 0.18 (range 0.05-0.83) and 0.08 (range light perception-0.72), respectively. Spectral-domain optical coherence tomography (SD-OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well-preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full-field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes.CONCLUSIONS: Despite the generally severe course of CRB1-RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.
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- 2021
29. Defining inclusion criteria and endpoints for clinical trials:a prospective cross-sectional study in CRB1-associated retinal dystrophies
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Talib, Mays, van Schooneveld, Mary J., Wijnholds, Jan, van Genderen, Maria M., Schalij-Delfos, Nicoline E., Talsma, Herman E., Florijn, Ralph J., ten Brink, Jacoline B., Cremers, Frans P.M., Thiadens, Alberta A.H.J., van den Born, L. Ingeborgh, Hoyng, Carel B., Meester-Smoor, Magda A., Bergen, Arthur A., Boon, Camiel J.F., Talib, Mays, van Schooneveld, Mary J., Wijnholds, Jan, van Genderen, Maria M., Schalij-Delfos, Nicoline E., Talsma, Herman E., Florijn, Ralph J., ten Brink, Jacoline B., Cremers, Frans P.M., Thiadens, Alberta A.H.J., van den Born, L. Ingeborgh, Hoyng, Carel B., Meester-Smoor, Magda A., Bergen, Arthur A., and Boon, Camiel J.F.
- Abstract
Purpose: To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints. Methods: In this prospective cross-sectional study, 22 patients with genetically confirmed CRB1-RD (aged 6–74 years), and who had a decimal best-corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full-field electroretinography (ERG) and full-field stimulus testing (FST). Ten patients were from a genetic isolate (GI). Results: Patients had retinitis pigmentosa (n = 19; GI and non-GI), cone-rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non-GI). Median age at first symptom onset was 3 years (range 0.8–49). Median decimal BCVA in the better and worse-seeing eye was 0.18 (range 0.05–0.83) and 0.08 (range light perception-0.72), respectively. Spectral-domain optical coherence tomography (SD-OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well-preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full-field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes. Conclusions: Despite the generally severe course of CRB1-RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.
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- 2021
30. CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF RHO-ASSOCIATED RETINITIS PIGMENTOSA: A Long-Term Follow-Up Study
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MS Oogheelkunde, Nguyen, Xuan Thanh An, Talib, Mays, van Cauwenbergh, Caroline, van Schooneveld, Mary J., Fiocco, Marta, Wijnholds, Jan, Ten Brink, Jacoline B., Florijn, Ralph J., Schalij-Delfos, Nicoline E., Dagnelie, Gislin, van Genderen, Maria M., de Baere, Elfride, Meester-Smoor, Magda A., De Zaeytijd, Julie, Balikova, Irina, Thiadens, Alberta A., Hoyng, Carel B., Klaver, Caroline C., van den Born, L. Ingeborgh, Bergen, Arthur A., Leroy, Bart P., Boon, Camiel J.F., MS Oogheelkunde, Nguyen, Xuan Thanh An, Talib, Mays, van Cauwenbergh, Caroline, van Schooneveld, Mary J., Fiocco, Marta, Wijnholds, Jan, Ten Brink, Jacoline B., Florijn, Ralph J., Schalij-Delfos, Nicoline E., Dagnelie, Gislin, van Genderen, Maria M., de Baere, Elfride, Meester-Smoor, Magda A., De Zaeytijd, Julie, Balikova, Irina, Thiadens, Alberta A., Hoyng, Carel B., Klaver, Caroline C., van den Born, L. Ingeborgh, Bergen, Arthur A., Leroy, Bart P., and Boon, Camiel J.F.
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- 2021
31. Genotype-phenotype correlation in pseudoxanthoma elasticum
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Researchgr. Systems Radiology, Oogheelkunde Onderzoek, MS Radiologie, Circulatory Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Beeldverwerking ISI, Other research (not in main researchprogram), Genetica, Genetica Klinische Genetica, Brain, Researchgr. Neuroradiologie, MS Oogheelkunde, MS Interne Geneeskunde, Bartstra, Jonas W., Risseeuw, Sara, de Jong, Pim A., van Os, Bram, Kalsbeek, Lianne, Mol, Chris, Baas, Annette F., Verschuere, Shana, Vanakker, Olivier, Florijn, Ralph J., Hendrikse, Jeroen, Mali, Willem, Imhof, Saskia, Ossewaarde-van Norel, Jeannette, van Leeuwen, Redmer, Spiering, Wilko, Researchgr. Systems Radiology, Oogheelkunde Onderzoek, MS Radiologie, Circulatory Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Beeldverwerking ISI, Other research (not in main researchprogram), Genetica, Genetica Klinische Genetica, Brain, Researchgr. Neuroradiologie, MS Oogheelkunde, MS Interne Geneeskunde, Bartstra, Jonas W., Risseeuw, Sara, de Jong, Pim A., van Os, Bram, Kalsbeek, Lianne, Mol, Chris, Baas, Annette F., Verschuere, Shana, Vanakker, Olivier, Florijn, Ralph J., Hendrikse, Jeroen, Mali, Willem, Imhof, Saskia, Ossewaarde-van Norel, Jeannette, van Leeuwen, Redmer, and Spiering, Wilko
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- 2021
32. Cone-rod dystrophy can be a manifestation of Danon disease
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Thiadens, Alberta A. H. J., Slingerland, Niki W. R., Florijn, Ralph J., Visser, Gerhard H., Riemslag, Frans C., and Klaver, Caroline C. W.
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- 2012
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33. Clinical course of cone dystrophy caused by mutations in the RPGR gene
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Thiadens, Alberta A. H. J., Soerjoesing, Gyan G., Florijn, Ralph J., Tjiam, A. G., den Hollander, Anneke I., van den Born, L. Ingeborgh, Riemslag, Frans C., Bergen, Arthur A. B., and Klaver, Caroline C. W.
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- 2011
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34. Mutations in TRPM1 are a common cause of complete congenital stationary night blindness
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van Genderen, Maria M., Bijveld, Mieke M.C., Claassen, Yvonne B., Florijn, Ralph J., Pearring, Jillian N., Meire, Francoise M., McCall, Maureen A., Riemslag, Frans C.C., Gregg, Ronald G., Bergen, Arthur A.B., and Kamermans, Maarten
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Gene mutations -- Analysis ,Night blindness -- Genetic aspects ,Night blindness -- Causes of ,Biological sciences - Abstract
Several studies are conducted to determine the causes, symptoms and characterization of the congenital stationary night blindness (CSNB), a clinically heterogeneous group of retinal disorders. The mutations taking place in the TRPM1 gene are shown to be the main cause of the disorder.
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- 2009
35. RPGR-Associated Dystrophies: Clinical, Genetic, and Histopathological Features
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Nguyen, Xuan-Thanh-An, Talib, Mays, van Schooneveld, Mary J, Brinks, Joost, Ten Brink, Jacoline, Florijn, Ralph J, Wijnholds, Jan, Verdijk, Robert M, Bergen, Arthur A, Boon, Camiel J F, Nguyen, Xuan-Thanh-An, Talib, Mays, van Schooneveld, Mary J, Brinks, Joost, Ten Brink, Jacoline, Florijn, Ralph J, Wijnholds, Jan, Verdijk, Robert M, Bergen, Arthur A, and Boon, Camiel J F
- Abstract
This study describes the clinical, genetic, and histopathological features in patients with RPGR-associated retinal dystrophies. Nine male patients from eight unrelated families underwent a comprehensive ophthalmic examination. Additionally, the histopathology of the right eye from a patient with an end-stage cone-rod-dystrophy (CRD)/sector retinitis pigmentosa (RP) phenotype was examined. All RPGR mutations causing a CRD phenotype were situated in exon ORF15. The mean best-corrected visual acuity (BCVA, decimals) was 0.58 (standard deviation (SD)): 0.34; range: 0.05-1.13); and the mean spherical refractive error was -4.1 D (SD: 2.11; range: -1.38 to -8.19). Hyperautofluorescent rings were observed in six patients. Full-field electroretinography responses were absent in all patients. The visual field defects ranged from peripheral constriction to central islands. The mean macular sensitivity on microperimetry was 11.6 dB (SD: 7.8; range: 1.6-24.4) and correlated significantly with BCVA (r = 0.907; p = 0.001). A histological examination of the donor eye showed disruption of retinal topology and stratification, with a more severe loss found in the peripheral regions. Reactive gliosis was seen in the inner layers of all regions. Our study demonstrates the highly variable phenotype found in RPGR-associated retinal dystrophies. Therapies should be applied at the earliest signs of photoreceptor degeneration, prior to the remodeling of the inner retina.
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- 2020
36. Defining inclusion criteria and endpoints for clinical trials: a prospective cross‐sectional study in CRB1 ‐associated retinal dystrophies
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Talib, Mays, primary, Schooneveld, Mary J., additional, Wijnholds, Jan, additional, Genderen, Maria M., additional, Schalij‐Delfos, Nicoline E., additional, Talsma, Herman E., additional, Florijn, Ralph J., additional, Brink, Jacoline B., additional, Cremers, Frans P.M., additional, Thiadens, Alberta A.H.J., additional, Born, L. Ingeborgh, additional, Hoyng, Carel B., additional, Meester‐Smoor, Magda A., additional, Bergen, Arthur A., additional, and Boon, Camiel J.F., additional
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- 2021
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37. Effective generation of very low density lipoprotein receptor transgenic mice by overlapping genomic DNA fragments: high testis expression and disturbed spermatogenesis
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Tacken, Paul J., Zee, Andre van der, Beumer, Tim L., Florijn, Ralph J., Gijpels, Marion J. J., Havekes, Louis M., Frants, Rune R., Dijk, Ko Willems van, and Hofker, Marten H.
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- 2001
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38. CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF RHO-ASSOCIATED RETINITIS PIGMENTOSA
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Nguyen, Xuan-Thanh-An, primary, Talib, Mays, additional, van Cauwenbergh, Caroline, additional, van Schooneveld, Mary J., additional, Fiocco, Marta, additional, Wijnholds, Jan, additional, ten Brink, Jacoline B., additional, Florijn, Ralph J., additional, Schalij-Delfos, Nicoline E., additional, Dagnelie, Gislin, additional, van Genderen, Maria M., additional, de Baere, Elfride, additional, Meester-Smoor, Magda A., additional, De Zaeytijd, Julie, additional, Balikova, Irina, additional, Thiadens, Alberta A., additional, Hoyng, Carel B., additional, Klaver, Caroline C., additional, van den Born, L. Ingeborgh, additional, Bergen, Arthur A., additional, Leroy, Bart P., additional, and Boon, Camiel J.F., additional
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- 2020
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39. RPGR-Associated Dystrophies: Clinical, Genetic, and Histopathological Features
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Nguyen, Xuan-Thanh-An, primary, Talib, Mays, additional, van Schooneveld, Mary J., additional, Brinks, Joost, additional, ten Brink, Jacoline, additional, Florijn, Ralph J., additional, Wijnholds, Jan, additional, Verdijk, Robert M., additional, Bergen, Arthur A., additional, and Boon, Camiel J.F., additional
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- 2020
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40. Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations
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Talib, Mays, van Schooneveld, Mary J, van Duuren, Roos J G, Van Cauwenbergh, Caroline, Ten Brink, Jacoline B, De Baere, Elfride, Florijn, Ralph J, Schalij-Delfos, Nicoline E, Leroy, Bart P, Bergen, Arthur A, Boon, Camiel J F, Talib, Mays, van Schooneveld, Mary J, van Duuren, Roos J G, Van Cauwenbergh, Caroline, Ten Brink, Jacoline B, De Baere, Elfride, Florijn, Ralph J, Schalij-Delfos, Nicoline E, Leroy, Bart P, Bergen, Arthur A, and Boon, Camiel J F
- Abstract
Purpose: To investigate the natural history in patients with LRAT-associated retinal degenerations (RDs), in the advent of clinical trials testing treatment options.Methods: A retrospective cohort of 13 patients with LRAT-RDs.Results: Twelve patients from a genetic isolate carried a homozygous c.12del mutation. One unrelated patient carried a homozygous c.326G>T mutation. The mean follow-up time was 25.3 years (SD 15.2; range 4.8-53.5). The first symptom was nyctalopia (n = 11), central vision loss (n = 1), or light-gazing (n = 1), and was noticed in the first decade of life. Seven patients (54%) reached low vision (visual acuity < 20/67), four of whom reaching blindness (visual acuity < 20/400), respectively, at mean ages of 49.9 (SE 5.4) and 59.9 (SE 3.1) years. The fundus appearance was variable. Retinal white dots were seen in six patients (46%). Full-field electroretinograms (n = 11) were nondetectable (n = 2; ages 31-60), reduced in a nonspecified pattern (n = 2; ages 11-54), or showed rod-cone (n = 6; ages 38-48) or cone-rod (n = 1; age 29) dysfunction. Optical coherence tomography (n = 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second (n = 1) and sixth decade of life (n = 2), and profound chorioretinal degeneration from the eighth decade of life (n = 1).Conclusions: LRAT-associated phenotypes in this cohort were variable and unusual, but generally milder than those seen in RPE65-associated disease, and may be particularly amenable to treatment. The window of therapeutic opportunity can be extended in patients with a mild phenotype.Translational Relevance: Knowledge of the natural history of LRAT-RDs is essential in determining the window of opportunity in ongoing and future clinical trials for novel therapeutic options.
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- 2019
41. CLINICAL and GENETIC CHARACTERISTICS of MALE PATIENTS with RPGR-ASSOCIATED RETINAL DYSTROPHIES: A Long-Term Follow-up Study
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MS Oogheelkunde, Talib, Mays, Van Schooneveld, Mary J., Thiadens, Alberta A., Fiocco, Marta, Wijnholds, Jan, Florijn, Ralph J., Schalij-Delfos, Nicoline E., Van Genderen, Maria M., Putter, Hein, Cremers, Frans P.M., Dagnelie, Gislin, Ten Brink, Jacoline B., Klaver, Caroline C.W., Van Den Born, L. Ingeborgh, Hoyng, Carel B., Bergen, Arthur A., Boon, Camiel J.F., MS Oogheelkunde, Talib, Mays, Van Schooneveld, Mary J., Thiadens, Alberta A., Fiocco, Marta, Wijnholds, Jan, Florijn, Ralph J., Schalij-Delfos, Nicoline E., Van Genderen, Maria M., Putter, Hein, Cremers, Frans P.M., Dagnelie, Gislin, Ten Brink, Jacoline B., Klaver, Caroline C.W., Van Den Born, L. Ingeborgh, Hoyng, Carel B., Bergen, Arthur A., and Boon, Camiel J.F.
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- 2019
42. Long-Term Follow-Up of Retinal Degenerations Associated WithLRATMutations and Their Comparability to Phenotypes Associated WithRPE65Mutations
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Talib, Mays, primary, van Schooneveld, Mary J., additional, van Duuren, Roos J. G., additional, Van Cauwenbergh, Caroline, additional, ten Brink, Jacoline B., additional, De Baere, Elfride, additional, Florijn, Ralph J., additional, Schalij-Delfos, Nicoline E., additional, Leroy, Bart P., additional, Bergen, Arthur A., additional, and Boon, Camiel J. F., additional
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- 2019
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43. The Phenotypic Spectrum of Albinism
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Kruijt, Charlotte C., primary, de Wit, Gerard C., additional, Bergen, Arthur A., additional, Florijn, Ralph J., additional, Schalij-Delfos, Nicoline E., additional, and van Genderen, Maria M., additional
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- 2018
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44. The phenotypic spectrum of albinism
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Kruijt, Charlotte, de Wit, Gerard C, Bergen, Arthur A, Florijn, Ralph J, Schalij-Delfos, Nicoline E, van Genderen, Maria M, Kruijt, Charlotte, de Wit, Gerard C, Bergen, Arthur A, Florijn, Ralph J, Schalij-Delfos, Nicoline E, and van Genderen, Maria M
- Abstract
PURPOSE: To describe the phenotypic spectrum of a large cohort of albino patients, to investigate the relationship between the ocular abnormalities and the visual acuity, and to define diagnostic criteria for the Caucasian population. We also estimated the prevalence of albinism in the Netherlands.DESIGN: Retrospective cohort study.SUBJECTS: We investigated the phenotype of 522 albinism patients from the databases of Bartiméus (452 patients), Leiden University Medical Center (44 patients) and the Academic Medical Center Amsterdam (26 patients).METHODS: We collected clinical, genetic and electrophysiological data of albinism patients. We used grading schemes for iris translucency, fundus hypopigmentation, and foveal hypoplasia.MAIN OUTCOME MEASURES: Visual acuity (VA), nystagmus, iris translucency, fundus pigmentation, foveal hypoplasia and misrouting.RESULTS: In 7.7% (40/521) nystagmus was absent, iris translucency could not be detected in 8.9% (44/492), 3.8% (19/496) had completely normal fundus pigmentation, 0.7% (3/455) had no foveal hypoplasia and in 16.1% (49/304) misrouting was not established. The VA varied from -0.1 to 1.3 logMAR. The foveal hypoplasia grading correlated best with the VA (r=0.69, p < 0.001), while iris translucency, fundus pigmentation and misrouting did not predict the VA significantly. We estimated a prevalence of albinism in the Netherlands of at least 1: 12 000.CONCLUSIONS: None of the characteristics of albinism were consistently present in our cohort. To be able to distinguish albinism from other conditions with similar ocular features, especially in northern and western European countries, we propose major and minor clinical criteria. Major criteria would be 1) foveal hypoplasia grade 2 or more, 2) misrouting, and 3) ocular hypopigmentation, either iris translucency or fundus hypopigmentation grade 2 or more. Minor criteria would be 1) nystagmus, 2) hypopigmentation of skin and hair, 3)
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- 2018
45. The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene
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Talib, Mays, van Schooneveld, Mary J, Van Cauwenbergh, Caroline, Wijnholds, Jan, Ten Brink, Jacoline B, Florijn, Ralph J, Schalij-Delfos, Nicoline E, Dagnelie, Gislin, van Genderen, Maria M, de Baere, Elfride, Meester-Smoor, Magda A, de Zaeytijd, Julie, Cremers, Frans P M, van den Born, L Ingeborgh, Thiadens, Alberta A, Hoyng, Carel B, Klaver, Caroline C, Leroy, Bart P, Bergen, Arthur A, Boon, Camiel J F, Talib, Mays, van Schooneveld, Mary J, Van Cauwenbergh, Caroline, Wijnholds, Jan, Ten Brink, Jacoline B, Florijn, Ralph J, Schalij-Delfos, Nicoline E, Dagnelie, Gislin, van Genderen, Maria M, de Baere, Elfride, Meester-Smoor, Magda A, de Zaeytijd, Julie, Cremers, Frans P M, van den Born, L Ingeborgh, Thiadens, Alberta A, Hoyng, Carel B, Klaver, Caroline C, Leroy, Bart P, Bergen, Arthur A, and Boon, Camiel J F
- Abstract
Purpose: The purpose of this study was to investigate the phenotype and long-term clinical course of female carriers of RPGR mutations.Methods: This was a retrospective cohort study of 125 heterozygous RPGR mutation carriers from 49 families.Results: Eighty-three heterozygotes were from retinitis pigmentosa (RP) pedigrees, 37 were from cone-/cone-rod dystrophy (COD/CORD) pedigrees, and 5 heterozygotes were from pedigrees with mixed RP/CORD or unknown diagnosis. Mutations were located in exon 1-14 and in ORF15 in 42 of 125 (34%) and 83 of 125 (66%) subjects, respectively. The mean age at the first examination was 34.4 years (range, 2.1 to 86.0 years). The median follow-up time in heterozygotes with longitudinal data (n = 62) was 12.2 years (range, 1.1 to 52.2 years). Retinal pigmentary changes were present in 73 (58%) individuals. Visual symptoms were reported in 51 (40%) cases. Subjects with both symptoms and pigmentary fundus changes were older than the other heterozygotes (P = 0.01) and had thinner foveal outer retinas (P = 0.006). Complete expression of the RP or CORD phenotype was observed in 29 (23%) heterozygotes, although usually in milder forms than in affected male relatives. Best-corrected visual acuity (BCVA) was <20/40 and <20/400 in at least one eye in 45 of 116 (39%) and 11 of 116 (9%) heterozygotes, respectively. Myopia was observed in 74 of 101 (73%) subjects and was associated with lower BCVA (P = 0.006). Increasing age was associated with lower BCVA (P = 0.002) and decreasing visual field size (P = 0.012; I4e isopter).Conclusions: RPGR mutations lead to a phenotypic spectrum in female carriers, with myopia as a significantly aggravating factor. Complete disease expression is observed in some individuals, who may benefit from future (gene) therapeutic options.
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- 2018
46. LONG-TERM FOLLOW-UP OF PATIENTS WITH CHOROIDEREMIA WITH SCLERAL PITS AND TUNNELS AS A NOVEL OBSERVATION
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van Schuppen, Sanne M, Talib, Mays, Bergen, Arthur A, Ten Brink, Jacoline B, Florijn, Ralph J, Boon, Camiel J F, van Schooneveld, Mary J, van Schuppen, Sanne M, Talib, Mays, Bergen, Arthur A, Ten Brink, Jacoline B, Florijn, Ralph J, Boon, Camiel J F, and van Schooneveld, Mary J
- Abstract
PURPOSE: To evaluate the long-term clinical course and visual outcome of patients with choroideremia.METHODS: Clinical examination, a social questionnaire, and medical records review of 21 patients with choroideremia from 14 families.RESULTS: The mean follow-up time was 25.2 years (SD: 13.3; range 2-57 years). The mean age at symptom onset was 15.1 years (SD: 10.1; range 5-40 years). Best-corrected visual acuity was stable until the age of 35 (P = 0.96), but declined significantly faster after the age of 35 (11%/year, P = 0.001), with a high variability between individual patients. The mean age at which patients discontinued working was 48.1 years (SD: 11.7, range 25-65 years). The reason for work discontinuation was vision related in 60% of cases. Most patients (70%) reported visual field constriction as the most debilitating symptom. The authors report scleral pits and tunnels as a novel finding visible on spectral domain optical coherence tomography and ophthalmoscopy.CONCLUSION: Choroideremia is a severely debilitating disease showing a rapid decline of visual acuity generally after the age of 35, but a more gradual decline for other abnormalities.
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- 2018
47. The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in theRPGRGene
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Talib, Mays, primary, van Schooneveld, Mary J., additional, Van Cauwenbergh, Caroline, additional, Wijnholds, Jan, additional, ten Brink, Jacoline B., additional, Florijn, Ralph J., additional, Schalij-Delfos, Nicoline E., additional, Dagnelie, Gislin, additional, van Genderen, Maria M., additional, De Baere, Elfride, additional, Meester-Smoor, Magda A., additional, De Zaeytijd, Julie, additional, Cremers, Frans P. M., additional, van den Born, L. Ingeborgh, additional, Thiadens, Alberta A., additional, Hoyng, Carel B., additional, Klaver, Caroline C., additional, Leroy, Bart P., additional, Bergen, Arthur A., additional, and Boon, Camiel J. F., additional
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- 2018
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48. Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study
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Talib, Mays, van Schooneveld, Mary J, van Genderen, Maria M, Wijnholds, Jan, Florijn, Ralph J, Ten Brink, Jacoline B, Schalij-Delfos, Nicoline E, Dagnelie, Gislin, Cremers, Frans P M, Wolterbeek, Ron, Fiocco, Marta, Thiadens, Alberta A, Hoyng, Carel B, Klaver, Caroline C, Bergen, Arthur A, Boon, Camiel J F, Talib, Mays, van Schooneveld, Mary J, van Genderen, Maria M, Wijnholds, Jan, Florijn, Ralph J, Ten Brink, Jacoline B, Schalij-Delfos, Nicoline E, Dagnelie, Gislin, Cremers, Frans P M, Wolterbeek, Ron, Fiocco, Marta, Thiadens, Alberta A, Hoyng, Carel B, Klaver, Caroline C, Bergen, Arthur A, and Boon, Camiel J F
- Abstract
PURPOSE: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies.DESIGN: Retrospective cohort study.PARTICIPANTS: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families.METHODS: A medical record review of 55 patients for age at onset, medical history, initial symptoms, best-corrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography.MAIN OUTCOME MEASURES: Age at onset, visual acuity survival time, visual acuity decline rate, and electroretinography and imaging findings.RESULTS: A retinitis pigmentosa (RP) phenotype was present in 50 patients, 34 of whom were from a Dutch genetic isolate (GI), and 5 patients had a Leber congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0-55.5 years). For the RP patients, the median age at symptom onset was 4.0 years. In the RP group, median ages for reaching low vision, severe visual impairment, and blindness were 18, 32, and 44 years, respectively, with a visual acuity decline rate of 0.03 logarithm of the minimum angle of resolution per year. The presence of a truncating mutation did not alter the annual decline rate significantly (P = 0.75). Asymmetry in visual acuity was found in 31% of patients. The annual VF decline rate was 5% in patients from the genetic isolate, which was significantly faster than in non-GI patients (P < 0.05). Full-field electroretinography responses were extinguished in 50% of patients, were pathologically attenuated without a documented rod or cone predominance in 30% of patients, and showed a rod-cone dysfunction pattern in 20% of RP patients. Cystoid fluid collections in the macula were found in 50% of RP patients.CONCLUSIONS: Mutations in the CRB1 gene are associated with a spectrum of progressive reti
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- 2017
49. LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS: A Severe Phenotype With Considerable Interindividual Variability
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Mathijssen, Inge B, Florijn, Ralph J, van den Born, L Ingeborgh, Zekveld-Vroon, Renate C, Ten Brink, Jacoline B, Plomp, Astrid S, Baas, Frank, Meijers-Heijboer, Hanne, Bergen, Arthur A B, van Schooneveld, Mary J, Mathijssen, Inge B, Florijn, Ralph J, van den Born, L Ingeborgh, Zekveld-Vroon, Renate C, Ten Brink, Jacoline B, Plomp, Astrid S, Baas, Frank, Meijers-Heijboer, Hanne, Bergen, Arthur A B, and van Schooneveld, Mary J
- Abstract
PURPOSE: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa.METHODS: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.(Met1041Thr) mutation from a Dutch genetically isolated population in which the CRB1 gene was originally identified. The authors evaluated medical records, analyzed a questionnaire, and performed a comprehensive ophthalmic examination, including optical coherence tomography.RESULTS: Mean follow-up was 19 years (range 0-45 years, SD 15 years). With aging, patients showed progressive visual decline, deterioration of visual fields, increasing narrowing of the anterior chamber, increased prevalence of cataract, and an increase in the amount of intraretinal pigmentations. Fifty percent of patients had a visual acuity of ≤0.3 at Age 18 and of ≤0.1 at Age 35. Electroretinogram responses were severely reduced or absent already at a young age and optical coherence tomography showed increased retinal thickness with often cystoid maculopathy at young age, and thinning of the retina and disorientation of the photoreceptor layer in the late stages. The clinical course showed considerable interindividual variability, but intraindividual similarity between both eyes was the rule.CONCLUSION: The wide and variable clinical spectrum in patients with the same CRB1 mutation supports the hypothesis that the CRB1 type autosomal recessive retinitis pigmentosa-phenotype is modulated by other factors. The clinical variability will make it harder to evaluate the effect of (upcoming) therapies for retinitis pigmentosa, although because of the intraindividual similarity between both eyes, the contralateral eye can be used as an excellent internal control.
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- 2017
50. ABCC6 mutations in pseudoxanthoma elasticum: an update including eight novel ones
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Plomp, Astrid S., Florijn, Ralph J., ten Brink, Jacoline, Castle, Bruce, Kingston, Helen, Martin-Santiago, Ana, Gorgels, Theo G. M. F., de Jong, Paulus T. V. M., Bergen, Arthur A. B., Human Genetics, Paediatric Genetics, Other departments, Ophthalmology, and ANS - Amsterdam Neuroscience
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Male ,Base Sequence ,Mutation, Missense ,Retina ,Mutation ,Humans ,Female ,Amino Acid Sequence ,Multidrug Resistance-Associated Proteins ,Pseudoxanthoma Elasticum ,Chromatography, High Pressure Liquid ,Conserved Sequence ,Gene Deletion ,Research Article ,Skin - Abstract
Purpose: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of connective tissue, affecting the retina, the skin, and the cardiovascular system. PXE is caused by mutations in ABCC6. Up to now, the literature reports that there are 180 different ABCC6 mutations in PXE. The purpose of this paper is to report eight novel mutations in ABCC6 and to update the spectrum and frequency of ABCC6 mutations in PXE patients. Methods: Eye, skin, and DNA examinations were performed using standard methodologies. We newly investigated the gene in 90 probands by denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. We examined a total of 166 probands. Results: Eight novel ABCC6 mutations (c.1685T>C, p.Met562Thr; c.2477T>C, p.Leu826Pro; c.2891G>C, p.Arg964Pro; c.3207C>A, p.Tyr1069X; c.3364delT, p.Ser1122fs; c.3717T>G, p.Tyr1293X; c.3871G>A, p.Ala1291Thr; c. 4306_4312del, p.Thr1436fs) were found in seven unrelated patients. Currently, our mutation detection score is at least one ABCC6 mutation in 87% of patients with a clinical diagnosis of PXE. Conclusions: Our results support that ABCC6 is the most important, and probably the only, causative gene of PXE. In total, 188 different ABCC6 mutations have now been reported in PXE in the literature
- Published
- 2008
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