136 results on '"Thong, Meow-Keong"'
Search Results
102. A tribute to Keiko Kobayashi and her work on citrin deficiency
- Author
-
Thong, Meow-Keong, primary
- Published
- 2012
- Full Text
- View/download PDF
103. Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients
- Author
-
Lee, Daphne SC, primary, Yoon, Sook-Yee, additional, Looi, Lai Meng, additional, Kang, Peter, additional, Kang, In Nee, additional, Sivanandan, Kavitta, additional, Ariffin, Hany, additional, Thong, Meow Keong, additional, Chin, Kin Fah, additional, Mohd Taib, Nur Aishah, additional, Yip, Cheng-Har, additional, and Teo, Soo-Hwang, additional
- Published
- 2012
- Full Text
- View/download PDF
104. Biochemical profiling of inborn errors of purine and pyrimidine metabolism by high-performance liquid chromatography – a strategy to improve childhood mortality and morbidity in Malaysian children
- Author
-
Thong Meow Keong, Zabedah M Yunus, and Chen Bee Chin
- Subjects
Purine ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,medicine.disease ,Gastroenterology ,Metabolism disorder ,chemistry.chemical_compound ,Dihydropyrimidine dehydrogenase deficiency ,chemistry ,Biochemistry ,Urea cycle ,Internal medicine ,Pyrimidine metabolism ,Adenylosuccinate ,medicine ,Uric acid ,education ,business - Abstract
Background . The epidemiology of inborn errors of purine and pyrimidine (PnP) metabolism in developing countries is unknown. Facilities for the analysis of PnP metabolites in Malaysia are currently lacking owing to limited resources and expertise in this field. To achieve the correct diagnosis for these disorders is a time-consuming and costly process. The tests are not readily available for our seriously ill patients. Objective . The primary aim of this study was to establish a simple and cost-effective method using rapid-resolution high-performance liquid chromatography (RR-HPLC) for the diagnosis of inborn errors of PnP metabolism among Malaysian children who are suspected to have disorders of PnP metabolism. The secondary aim was to study the epidemiology and biochemical phenotype in our patients. Methods . The analytical method was developed using a reversed-phase high-performance liquid chromatography (RP-HPLC) with C18 column coupled to a diode array detector for simultaneous determination of the PnP metabolites. A total of 1499 patients were studied. 556 healthy children and adults were recruited as normal controls to establish age-related reference ranges and urinary uric acid – creatinine ratios. Results . The method established was able to separate up to 18 PnP metabolites in a single analytical run time of 28 minutes. Good precision (coefficient variation of 0.9993) was also observed. Recoveries were 99.8–108.4% for the tested metabolites. The detection limit of 2.18–12.5 μmol/l was adequate to detect patients with slightly increased concentration of these metabolites. Agerelated reference ranges among our population were established and were used for diagnostic interpretation related to this group of disorders. Twelve patients (0.8%) were diagnosed, including four with combined molybdenum cofactor deficiency, three with isolated sulphite oxidase deficiency, two with thymidine phosphorylase deficiency, one with adenylosuccinate lyase deficiency and two with dihydropyrimidine dehydrogenase deficiency. Four cases of urea cycle defects were also detected. Conclusions . The method that we developed was proven to be efficient, reliable and sensitive enough to be applied in our clinical laboratory for the diagnosis of inborn errors of PnP metabolism disorders among Malaysian children. Early recognition and correct diagnosis allowed prompt treatment, better outcome and genetic counselling.
- Published
- 2012
105. Diagnosis and management of Duchenne muscular dystrophy in a developing country over a 10-year period
- Author
-
Thong, Meow-Keong, primary, Bazlin, RI Raja, additional, and Wong, Kum-Thong, additional
- Published
- 2007
- Full Text
- View/download PDF
106. Diagnosis and management of Duchenne muscular dystrophy in a developing country over a 10-year period
- Author
-
Thong, Meow-Keong, primary, Raja Bazlin, RI, additional, and Wong, Kum-Thong, additional
- Published
- 2005
- Full Text
- View/download PDF
107. Further delineation of Al-Gazali syndrome (multiple skeletal abnormalities with anterior segment anomalies of the eye and early lethality) in a Malaysian family
- Author
-
Thong, Meow-Keong, primary, Chan, Lee-Gaik, additional, and Ting, Hua-Sen, additional
- Published
- 2005
- Full Text
- View/download PDF
108. Effects ofMECP2mutation type, location and X‐inactivation in modulating Rett syndrome phenotype
- Author
-
Weaving, Linda S., primary, Williamson, Sarah L., additional, Bennetts, Bruce, additional, Davis, Mark, additional, Ellaway, Carolyn J., additional, Leonard, Helen, additional, Thong, Meow‐Keong, additional, Delatycki, Martin, additional, Thompson, Elizabeth M., additional, Laing, Nigel, additional, and Christodoulou, John, additional
- Published
- 2002
- Full Text
- View/download PDF
109. Ten novelFBN2mutations in congenital contractural arachnodactyly: Delineation of the molecular pathogenesis and clinical phenotype
- Author
-
Gupta, Prateek A., primary, Putnam, Elizabeth A., additional, Carmical, Sonya G., additional, Kaitila, Ilkka, additional, Steinmann, Beat, additional, Child, Anne, additional, Danesino, Cesare, additional, Metcalfe, Kay, additional, Berry, Susan A., additional, Chen, Emily, additional, Delorme, Catherine Vincent, additional, Thong, Meow-Keong, additional, Adès, Lesley C., additional, and Milewicz, Dianna M., additional
- Published
- 2001
- Full Text
- View/download PDF
110. Acampomelic campomelic dysplasia with SOX9 mutation
- Author
-
Thong, Meow‐Keong, primary, Scherer, Gerd, additional, Kozlowski, Kazimierz, additional, Haan, Eric, additional, and Morris, Lloyd, additional
- Published
- 2000
- Full Text
- View/download PDF
111. Acampomelic campomelic dysplasia withSOX9 mutation
- Author
-
Thong, Meow-Keong, primary, Scherer, Gerd, additional, Kozlowski, Kazimierz, additional, Haan, Eric, additional, and Morris, Lloyd, additional
- Published
- 2000
- Full Text
- View/download PDF
112. A child with hemimegalencephaly, hemihypertrophy, macrocephaly, cutaneous vascular malformation, psychomotor retardation and intestinal lymphangiectasia???a diagnostic dilemma
- Author
-
Thong, Meow-Keong, primary, Thompson, Elizabeth, additional, Keenan, Ross, additional, Simmer, Karen, additional, Harbord, Michael, additional, Davidson, Geoffrey, additional, and Haan, Eric, additional
- Published
- 1999
- Full Text
- View/download PDF
113. Genetic Polymorphisms in LDLR, APOB, PCSK9 and Other Lipid Related Genes Associated with Familial Hypercholesterolemia in Malaysia.
- Author
-
Lye, Say-Hean, Chahil, Jagdish Kaur, Bagali, Pramod, Alex, Livy, Vadivelu, Jamunarani, Ahmad, Wan Azman Wan, Chan, Siew-Pheng, Thong, Meow-Keong, Zain, Shamsul Mohd, and Mohamed, Rosmawati
- Subjects
GENETIC polymorphisms ,LIPIDS ,HYPERCHOLESTEREMIA ,APOLIPOPROTEIN B ,POPULATION genetics ,GENETIC mutation - Abstract
Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevations in total cholesterol (TC) and low density lipoprotein cholesterol (LDLc). Development of FH can result in the increase of risk for premature cardiovascular diseases (CVD). FH is primarily caused by genetic variations in Low Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB) or Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) genes. Although FH has been extensively studied in the Caucasian population, there are limited reports of FH mutations in the Asian population. We investigated the association of previously reported genetic variants that are involved in lipid regulation in our study cohort. A total of 1536 polymorphisms previously implicated in FH were evaluated in 141 consecutive patients with clinical FH (defined by the Dutch Lipid Clinic Network criteria) and 111 unrelated control subjects without FH using high throughput microarray genotyping platform. Fourteen Single Nucleotide Polymorphisms (SNPs) were found to be significantly associated with FH, eleven with increased FH risk and three with decreased FH risk. Of the eleven SNPs associated with an increased risk of FH, only one SNP was found in the LDLR gene, seven in the APOB gene and three in the PCSK9 gene. SNP rs12720762 in APOB gene is associated with the highest risk of FH (odds ratio 14.78, p<0.001). Amongst the FH cases, 108 out of 141 (76.60%) have had at least one significant risk-associated SNP. Our study adds new information and knowledge on the genetic polymorphisms amongst Asians with FH, which may serve as potential markers in risk prediction and disease management. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
114. Ten novel FBN2 mutations in congenital contractural arachnodactyly: Delineation of the molecular pathogenesis and clinical phenotype.
- Author
-
Gupta, Prateek A., Putnam, Elizabeth A., Carmical, Sonya G., Kaitila, Ilkka, Steinmann, Beat, Child, Anne, Danesino, Cesare, Metcalfe, Kay, Berry, Susan A., Chen, Emily, Delorme, Catherine Vincent, Thong, Meow-Keong, Adès, Lesley C., and Milewicz, Dianna M.
- Published
- 2002
- Full Text
- View/download PDF
115. Effects of <TOGGLE>MECP2</TOGGLE> mutation type, location and X-inactivation in modulating Rett syndrome phenotype
- Author
-
Weaving, Linda S., Williamson, Sarah L., Bennetts, Bruce, Davis, Mark, Ellaway, Carolyn J., Leonard, Helen, Thong, Meow-Keong, Delatycki, Martin, Thompson, Elizabeth M., and Laing, Nigel
- Abstract
Rett syndrome (RTT) is a clinically defined disorder that describes a subset of patients with mutations in the X-linked MECP2 gene. However, there is a high degree of variability in the clinical phenotypes produced by mutations in MECP2, even amongst classical RTT patients. In a large-scale screening project, this variability has been examined by looking at the effects of mutation type, functional domain affected and X-inactivation. Mutations have been identified in 60% of RTT patients in this study (25% of whom were atypical), including 23 novel mutations and polymorphisms. More mutations were found in classical patients (63%) compared to atypical patients (44%). All of the pathogenic mutations were de novo in patients for whom parent DNA was available for screening. A composite phenotype score was developed, based on the recommendations for reporting clinical features in RTT of an international collaborative group. This score proved useful for summarising phenotypic severity, but did not correlate with mutation type, domain affected or X-inactivation, probably due to complex interactions between all three. Other correlations suggested that truncating mutations and mutations affecting the methyl-CpG-binding domain tend to lead to a more severe phenotype. Skewed X-inactivation was found in a large proportion (43%) of our patients, particularly in those with truncating mutations and mutations affecting the MBD. It is therefore likely that X-inactivation does modulate the phenotype in RTT. © 2003 Wiley-Liss, Inc.
- Published
- 2003
- Full Text
- View/download PDF
116. Acampomelic campomelic dysplasia with <TOGGLE>SOX9</TOGGLE> mutation
- Author
-
Thong, Meow-Keong, Scherer, Gerd, Kozlowski, Kazimierz, Haan, Eric, and Morris, Lloyd
- Abstract
Acampomelic campomelic dysplasia is a rare clinical variant of the more commonly encountered campomelic dysplasia (CMD1), characterized by absence of long bone curvature (acampomelia). We present a patient with acampomelic CMD1 with a de novo SOX9 missense mutation and report his clinical course to age one year, thereby contributing to genotype-phenotype correlation in CMD1. Am. J. Med. Genet. 93:421425, 2000. © 2000 Wiley-Liss, Inc.
- Published
- 2000
- Full Text
- View/download PDF
117. Exercise induced cramps and myoglobinuria in dystrophinopathy - a report of three Malaysian patients
- Author
-
Annuar, Azlina Ahmad, Wong, Kum Thong, Ching, Ai Sze, Thong, Meow Keong, Wong, Sau Wei, Alsiddiq, Feizel, Ong, Lai Choo, and Goh, Khean Jin
118. Methylmalonic Aciduria: A Treatable Disorder of Which Adult Neurologists Need to Be Aware.
- Author
-
Tan, Ai Huey, Mah, Jordina Siu Yi, Thong, Meow Keong, and Lim, Shen‐Yang
- Subjects
METHYLMALONIC acid ,AMINO acid metabolism ,NEUROLOGY hospitals ,NEUROLOGISTS ,MAGNETIC resonance imaging ,DEFICIT awareness - Abstract
The article presents a case study of a 28-year-old woman who had an isolated methylmalonic aciduria (MMA), an autosomal-recessive disorder of amino acid metabolism and it needs to be address to the adult neurology service. She had no other relevant family history after presented with seizures and generalized dystonia. She undergone brain magnetic resonance imaging (MRI) wherein the findings shown striking pallidal hyperintensity. Also mentions the prevalence of the isolated MMA.
- Published
- 2016
- Full Text
- View/download PDF
119. Prevalence of PALB2 Mutations in Breast Cancer Patients in Multi-Ethnic Asian Population in Malaysia and Singapore.
- Author
-
Phuah, Sze Yee, Lee, Sheau Yee, Kang, Peter, Kang, In Nee, Yoon, Sook-Yee, Thong, Meow Keong, Hartman, Mikael, Sng, Jen-Hwei, Yip, Cheng Har, Taib, Nur Aishah Mohd, and Teo, Soo-Hwang
- Subjects
DISEASE prevalence ,GENETICS of breast cancer ,GENETIC mutation ,ETHNICITY ,ASIANS ,DISEASES - Abstract
Background:The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations. Methods:We evaluated the contribution of PALB2 germline mutations in 122 Asian women with breast cancer, all of whom had significant family history of breast and other cancers. Further screening for nine PALB2 mutations was conducted in 874 Malaysian and 532 Singaporean breast cancer patients, and in 1342 unaffected Malaysian and 541 unaffected Singaporean women. Results:By analyzing the entire coding region of PALB2, we found two novel truncating mutations and ten missense mutations in families tested negative for BRCA1/2-mutations. One additional novel truncating PALB2 mutation was identified in one patient through genotyping analysis. Our results indicate a low prevalence of deleterious PALB2 mutations and a specific mutation profile within the Malaysian and Singaporean populations. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
120. β-Thalassemias.
- Author
-
Meow-Keong Thong, Chin-Fang Ngim, Thong, Meow-Keong, and Ngim, Chin-Fang
- Subjects
- *
ALPHA-Thalassemia , *PRENATAL diagnosis , *BETA-Thalassemia - Published
- 2021
- Full Text
- View/download PDF
121. Rubinstein-Taybi syndrome in diverse populations
- Author
-
Leah Dowsett, Omar A. Abdul-Rahman, Kelly L. Jones, Nicole Fleischer, Leon Mutesa, Babajide Owosela, María Gabriela Obregon, Victoria Huckstadt, Ebenezer Badoe, Bryan Malonga, Ekanem N. Ekure, Neerja Gupta, Ho Ming Luk, Gerarda Cappuccio, Engy A. Ashaat, Alicia Diaz-Kuan, Mona O. El Ruby, Jasmine L.F. Fung, Paul Kruszka, Stephanie Lotz-Esquivel, Nirmala D. Sirisena, Monica Penon Portmann, Carolyn Sian Kitchin, Cedrik Tekendo-Ngongang, Ifeanyi Kanayo Ifeorah, Meow-Keong Thong, Annette Uwineza, Sansan Lee, Yonit A. Addissie, Brian H.Y. Chung, Ivan F M Lo, Dalia Farouk Hussen, Angélica Moresco, Vajira H. W. Dissanayake, Maximilian Muenke, Nicola Brunetti-Pierri, Eloise J. Prijoles, Ramses Badilla-Porras, Roger E. Stevenson, Leticia Cassimiro Batista, Manuel Saborio-Rocafort, Danilo Moretti-Ferreira, Arianne Llamos Paneque, Tekendo-Ngongang, Cedrik, Owosela, Babajide, Fleischer, Nicole, Addissie, Yonit A, Malonga, Bryan, Badoe, Ebenezer, Gupta, Neerja, Moresco, Angélica, Huckstadt, Victoria, Ashaat, Engy A, Hussen, Dalia Farouk, Luk, Ho-Ming, Lo, Ivan F M, Hon-Yin Chung, Brian, Fung, Jasmine L F, Moretti-Ferreira, Danilo, Batista, Letícia Cassimiro, Lotz-Esquivel, Stephanie, Saborio-Rocafort, Manuel, Badilla-Porras, Ramse, Penon Portmann, Monica, Jones, Kelly L, Abdul-Rahman, Omar A, Uwineza, Annette, Prijoles, Eloise J, Ifeorah, Ifeanyi Kanayo, Llamos Paneque, Arianne, Sirisena, Nirmala D, Dowsett, Leah, Lee, Sansan, Cappuccio, Gerarda, Kitchin, Carolyn Sian, Diaz-Kuan, Alicia, Thong, Meow-Keong, Obregon, María Gabriela, Mutesa, Leon, Dissanayake, Vajira H W, El Ruby, Mona O, Brunetti-Pierri, Nicola, Ekure, Ekanem Nsikak, Stevenson, Roger E, Muenke, Maximilian, Kruszka, Paul, The National Institutes of Health, FDNA Inc., College of Health Sciences, All India Institute of Medical Sciences, Hospital de Pediatría Garrahan, National Research Centre, Hong Kong Special Administrative Region, Universidade Estadual Paulista (Unesp), Hospital San Juan de Dios (CCSS), National Children's Hospital Dr. Carlos Sáenz Herrera (CCSS), University of California San Francisco, Children's Hospital of The King's Daughters, University of Nebraska Medical Center, University of Rwanda, Greenwood Genetic Center, Nigerian Air Force, School of Dentistry, University of Colombo, Kapi'olani Medical Center and University of Hawai'i, Federico II University, Telethon Institute of Genetics and Medicine (TIGEM), University of Cape Town, Instituto de Medicina Genética, University of Malaya, University of Lagos, and American College of Medical Genetics and Genomics
- Subjects
Adult ,Male ,Rubinstein–Taybi syndrome ,Pediatrics ,medicine.medical_specialty ,Asia ,Adolescent ,Population ,facial analysis technology ,Physical examination ,African Group ,European descent ,Cohort Studies ,Middle East ,Young Adult ,Intellectual disability ,Genetics ,medicine ,Ethnicity ,Humans ,Craniofacial ,education ,Child ,Genetics (clinical) ,Genetic Association Studies ,Rubinstein-Taybi Syndrome ,education.field_of_study ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,Infant ,International Agencies ,Middle Aged ,medicine.disease ,Prognosis ,Latin America ,Genetics, Population ,Case-Control Studies ,Child, Preschool ,Face ,Africa ,Mutation ,Female ,business ,E1A-Associated p300 Protein - Abstract
Made available in DSpace on 2021-06-25T10:11:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 National Human Genome Research Institute Rubinstein–Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p
- Published
- 2020
122. The frequency of common mitochondrial DNA mutations in a cohort of Malaysian patients with specific mitochondrial encephalomyopathy syndromes.
- Author
-
Chong, Jia-Woei, Annuar, Azlina Ahmad, Wong, Kum-Thong, Thong, Meow-Keong, and Goh, Khean-Jin
- Subjects
- *
MERRF syndrome , *EPILEPSY , *BRAIN diseases , *SPASMS , *DNA - Abstract
A cohort of Malaysian patients with clinico-pathological diagnosis of three specifi c mitochondrial encephalomyopathy syndromes comprising of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy with ragged-red fibers (MERRF) and Leigh syndrome were studied to determine the frequency of their common mitochondrial DNA mutations. The 'hot-spot' point mutations for MELAS, MERRF and Leigh syndrome were screened. In the absence of common point mutations, screening of large-scale deletions as well as sequencing of tRNALeu and tRNALys genes were performed. Of 22 patients studied, nine m.3243A>G mutations, four m.8344A>G mutations, one m.8993T>G mutation and one deletion were identified (65% detection rate). While the m.3243A>G mutation was closely associated with MELAS, the m.8344A>G was more heterogenous, being seen in one MERFF, two isolated mitochondrial myopathies and one Leigh syndrome patient. Screening for m.8993T>G in Leigh syndrome has a low yield as unsurprisingly Leigh syndrome has considerable genetic heterogeneity. [ABSTRACT FROM AUTHOR]
- Published
- 2011
123. Global Globin Network and adopting genomic variant database requirements for thalassemia.
- Author
-
Halim-Fikri H, Zulkipli NN, Alauddin H, Bento C, Lederer CW, Kountouris P, Kleanthous M, Hernaningsih Y, Thong MK, Mahmood MH, Mohd Yasin N, Esa E, Elion J, Coviello D, Raja-Sabudin RZ, El-Kamah G, Burn J, Mohd Yusoff N, Ramesar R, and Zilfalil BA
- Subjects
- Humans, Globins genetics, Genomics methods, Genetic Variation, Thalassemia genetics, Databases, Genetic
- Abstract
Thalassemia is one of the most prevalent monogenic disorders in low- and middle-income countries (LMICs). There are an estimated 270 million carriers of hemoglobinopathies (abnormal hemoglobins and/or thalassemia) worldwide, necessitating global methods and solutions for effective and optimal therapy. LMICs are disproportionately impacted by thalassemia, and due to disparities in genomics awareness and diagnostic resources, certain LMICs lag behind high-income countries (HICs). This spurred the establishment of the Global Globin Network (GGN) in 2015 at UNESCO, Paris, as a project-wide endeavor within the Human Variome Project (HVP). Primarily aimed at enhancing thalassemia clinical services, research, and genomic diagnostic capabilities with a focus on LMIC needs, GGN aims to foster data collection in a shared database by all affected nations, thus improving data sharing and thalassemia management. In this paper, we propose a minimum requirement for establishing a genomic database in thalassemia based on the HVP database guidelines. We suggest using an existing platform recommended by HVP, the Leiden Open Variation Database (LOVD) (https://www.lovd.nl/). Adoption of our proposed criteria will assist in improving or supplementing the existing databases, allowing for better-quality services for individuals with thalassemia. Database URL: https://www.lovd.nl/., (© The Author(s) 2024. Published by Oxford University Press.)
- Published
- 2024
- Full Text
- View/download PDF
124. Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study.
- Author
-
Tan YT, Azanan MS, Hng SY, Eg KP, Jalaludin MY, Thong MK, Tae SK, Samingan N, Anuar A, and Nathan AM
- Subjects
- Humans, Retrospective Studies, Male, Female, Malaysia epidemiology, Child, Child, Preschool, Insulin-Like Growth Factor I, Treatment Outcome, Infant, Prader-Willi Syndrome drug therapy, Prader-Willi Syndrome complications, Sleep Apnea Syndromes drug therapy, Human Growth Hormone therapeutic use, Polysomnography
- Abstract
Study Objectives: The effect of recombinant human growth hormone (rhGH) on sleep-disordered breathing (SDB) in Malaysian children with Prader-Willi syndrome (PWS) is under-investigated. We determined (1) the short- and long-term effects of rhGH and (2) factors associated with worsening SDB in children with PWS receiving rhGH., Methods: This retrospective study included children with PWS (with and without rhGH) who had undergone at least 1 polysomnography. Outcomes measured were the presence of SDB before and after starting rhGH and the progress of SDB with and without rhGH. Serial insulin-like growth factor 1 (IGF-1) measurements were recorded., Results: One-hundred and thirteen polysomnograms were analyzed. The majority (92.3%) of initial polysomnograms showed SDB, with a median (interquartile range) apnea-hypopnea index of 5.0 (2.6, 16.3) events/h. The age for receiving rhGH was a median (IQR) of 1.9 (0.7, 3.4) years. One-third (36.8%) had worsening SDB after initiating rhGH, which was associated with higher IGF-1 levels post-rhGH ( P = .007). After a median of 5 years of rhGH, 73.6% maintained or reduced their positive airway pressure settings. Without rhGH, 80% had increased their positive airway pressure settings. Worsening SDB while on rhGH was associated with higher body mass index, lower rhGH dose, higher IGF-1 levels, and non-15q deletion., Conclusions: The majority of Malaysian children with PWS had SDB. At initiation of rhGH, one-third of patients had worsening SDB, associated with increased IGF-1 levels. Stabilization of SDB was more frequently seen in those receiving long-term rhGH. Worsening SDB while on rhGH was associated with a higher body mass index, receiving a lower dose of rhGH, higher IGF-1 levels, and non-15q deletion., Citation: Tan YT, Azanan MS, Hng SY, et al. Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study. J Clin Sleep Med . 2024;20(8):1291-1299., (© 2024 American Academy of Sleep Medicine.)
- Published
- 2024
- Full Text
- View/download PDF
125. GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases.
- Author
-
Lesmann H, Hustinx A, Moosa S, Klinkhammer H, Marchi E, Caro P, Abdelrazek IM, Pantel JT, Hagen MT, Thong MK, Binti Mazlan RA, Tae SK, Kamphans T, Meiswinkel W, Li JM, Javanmardi B, Knaus A, Uwineza A, Knopp C, Tkemaladze T, Elbracht M, Mattern L, Jamra RA, Velmans C, Strehlow V, Jacob M, Peron A, Dias C, Nunes BC, Vilella T, Pinheiro IF, Kim CA, Melaragno MI, Weiland H, Kaptain S, Chwiałkowska K, Kwasniewski M, Saad R, Wiethoff S, Goel H, Tang C, Hau A, Barakat TS, Panek P, Nabil A, Suh J, Braun F, Gomy I, Averdunk L, Ekure E, Bergant G, Peterlin B, Graziano C, Gaboon N, Fiesco-Roa M, Spinelli AM, Wilpert NM, Phowthongkum P, Güzel N, Haack TB, Bitar R, Tzschach A, Rodriguez-Palmero A, Brunet T, Rudnik-Schöneborn S, Contreras-Capetillo SN, Oberlack A, Samango-Sprouse C, Sadeghin T, Olaya M, Platzer K, Borovikov A, Schnabel F, Heuft L, Herrmann V, Oegema R, Elkhateeb N, Kumar S, Komlosi K, Mohamed K, Kalantari S, Sirchia F, Martinez-Monseny AF, Höller M, Toutouna L, Mohamed A, Lasa-Aranzasti A, Sayer JA, Ehmke N, Danyel M, Sczakiel H, Schwartzmann S, Boschann F, Zhao M, Adam R, Einicke L, Horn D, Chew KS, Kam CC, Karakoyun M, Pode-Shakked B, Eliyahu A, Rock R, Carrion T, Chorin O, Zarate YA, Conti MM, Karakaya M, Tung ML, Chandra B, Bouman A, Lumaka A, Wasif N, Shinawi M, Blackburn PR, Wang T, Niehues T, Schmidt A, Roth RR, Wieczorek D, Hu P, Waikel RL, Ledgister Hanchard SE, Elmakkawy G, Safwat S, Ebstein F, Krüger E, Küry S, Bézieau S, Arlt A, Olinger E, Marbach F, Li D, Dupuis L, Mendoza-Londono R, Houge SD, Weis D, Chung BH, Mak CCY, Kayserili H, Elcioglu N, Aykut A, Şimşek-Kiper PÖ, Bögershausen N, Wollnik B, Bentzen HB, Kurth I, Netzer C, Jezela-Stanek A, Devriendt K, Gripp KW, Mücke M, Verloes A, Schaaf CP, Nellåker C, Solomon BD, Nöthen MM, Abdalla E, Lyon GJ, Krawitz PM, and Hsieh TC
- Abstract
The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.
- Published
- 2024
- Full Text
- View/download PDF
126. Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants - an Asian study of 572 families.
- Author
-
Ho WK, Hassan NT, Yoon SY, Yang X, Lim JMC, Binte Ishak ND, Ho PJ, Wijaya EA, Ng PP, Luccarini C, Allen J, Tai MC, Chiang J, Zhang Z, See MH, Thong MK, Woo YL, Dunning AM, Hartman M, Yip CH, Mohd Taib NA, Easton DF, Li J, Ngeow J, Antoniou AC, and Teo SH
- Abstract
Background: Clinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia., Methods: Data were collected on 271 BRCA1 and 301 BRCA2 families from Malaysia and Singapore, ascertained through population/hospital-based case-series (88%) and genetic clinics (12%). Age-specific cancer risks were estimated using a modified segregation analysis method, adjusted for ascertainment., Findings: BC and OC relative risks (RRs) varied across age groups for both BRCA1 and BRCA 2. The age-specific RR estimates were similar across ethnicities and country of residence. For BRCA1 carriers of Malay, Indian and Chinese ancestry born between 1950 and 1959 in Malaysia, the cumulative risk (95% CI) of BC by age 80 was 40% (36%-44%), 49% (44%-53%) and 55% (51%-60%), respectively. The corresponding estimates for BRCA2 were 29% (26-32%), 36% (33%-40%) and 42% (38%-45%). The corresponding cumulative BC risks for Singapore residents from the same birth cohort, where the underlying population cancer incidences are higher compared to Malaysia, were higher, varying by ancestry group between 57 and 61% for BRCA1, and between 43 and 47% for BRCA2 carriers. The cumulative risk of OC by age 80 was 31% (27-36%) for BRCA1 and 12% (10%-15%) for BRCA2 carriers in Malaysia born between 1950 and 1959; and 42% (34-50%) for BRCA1 and 20% (14-27%) for BRCA2 carriers of the same birth cohort in Singapore. There was evidence of increased BC and OC risks for women from >1960 birth cohorts (p-value = 3.6 × 10
-5 for BRCA1 and 0.018 for BRCA 2)., Interpretation: The absolute age-specific cancer risks of Asian carriers vary depending on the underlying population-specific cancer incidences, and hence should be customised to allow for more accurate cancer risk management., Funding: Wellcome Trust [grant no: v203477/Z/16/Z]; CRUK (PPRPGM-Nov20∖100002)., Competing Interests: Z.Z received honorarium from AstraZeneca. J.N received research funding from AstraZeneca and MiRXES. A.C.A is listed as creator of the BOADICEA model which has been licensed by Cambridge Enterprise, from which University of Cambridge may receive royalties. N.A.M.T received honoraria for lectures from Zuellig Pharma Sdn Bhd and Astra Zeneca, received support for attending meetings and/or travel from MSD and Astra Zeneca. S.Y.Y received speaker's honoraria from Astra Zeneca, she is the president of Genetic Counselling Society Malaysia., (© 2024 The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
127. Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes.
- Author
-
Yoon SY, Wong SW, Lim J, Ahmad S, Mariapun S, Padmanabhan H, Hassan NT, Lau SY, Ch'ng GS, Haniffa M, Ong WP, Rethanavelu K, Moey LH, Keng WT, Omar J, Mohd Abas MN, Yong CM, Ramasamy V, Md Noor MR, Aliyas I, Lim MCK, Suberamaniam A, Mat Adenan NA, Ahmad ZA, Ho GF, Abdul Malik R, Subramaniam S, Khoo BP, Raja A, Chin YS, Sim WW, Teh BH, Kho SK, Ong ESE, Voon PJ, Ismail G, Lee CL, Abdullah BZ, Loo KS, Lim CS, Lee SJ, Lim KJL, Shafiee MN, Ismail F, Latiff ZA, Ismail MP, Mohamed Jamli MF, Kumarasamy S, Leong KW, Low J, Md Yusof M, Ahmad Mustafa AM, Mat Ali NH, Makanjang M, Tayib S, Cheah N, Lim BK, Fong CK, Foo YC, Mellor Abdullah M, Tan TS, Chow DSY, Ho KF, Raman R, Radzi A, Deniel A, Teoh DCY, Ang SF, Joseph JK, Ng PHO, Tho LM, Ahmad AR, Muin I, Bleiker E, George A, Thong MK, Woo YL, and Teo SH
- Subjects
- BRCA1 Protein genetics, BRCA2 Protein genetics, Counseling, Female, Genetic Counseling, Genetic Testing methods, Humans, Prospective Studies, Oncologists, Ovarian Neoplasms diagnosis, Ovarian Neoplasms epidemiology, Ovarian Neoplasms genetics
- Abstract
Background: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming., Methods: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer., Results: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms., Conclusion: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
- Full Text
- View/download PDF
128. β-Thalassemias.
- Author
-
Thong MK and Ngim CF
- Subjects
- Female, Humans, Pregnancy, Prenatal Diagnosis, alpha-Thalassemia, beta-Thalassemia diagnosis, beta-Thalassemia therapy
- Published
- 2021
- Full Text
- View/download PDF
129. Turner syndrome in diverse populations.
- Author
-
Kruszka P, Addissie YA, Tekendo-Ngongang C, Jones KL, Savage SK, Gupta N, Sirisena ND, Dissanayake VHW, Paththinige CS, Aravena T, Nampoothiri S, Yesodharan D, Girisha KM, Patil SJ, Jamuar SS, Goh JC, Utari A, Sihombing N, Mishra R, Chitrakar NS, Iriele BC, Lulseged E, Megarbane A, Uwineza A, Oyenusi EE, Olopade OB, Fasanmade OA, Duenas-Roque MM, Thong MK, Tung JYL, Mok GTK, Fleischer N, Rwegerera GM, de Herreros MB, Watts J, Fieggen K, Huckstadt V, Moresco A, Obregon MG, Hussen DF, Ashaat NA, Ashaat EA, Chung BHY, Badoe E, Faradz SMH, El Ruby MO, Shotelersuk V, Wonkam A, Ekure EN, Phadke SR, Richieri-Costa A, and Muenke M
- Subjects
- Abnormalities, Multiple diagnosis, Abnormalities, Multiple genetics, Abnormalities, Multiple physiopathology, Adolescent, Adult, Asian People genetics, Child, Child, Preschool, Chromosomes, Human, X genetics, Face pathology, Facial Recognition, Female, Hispanic or Latino genetics, Humans, Infant, Infant, Newborn, Male, Middle Aged, Noonan Syndrome diagnosis, Noonan Syndrome genetics, Noonan Syndrome physiopathology, Phenotype, Population Surveillance, Turner Syndrome diagnosis, Turner Syndrome genetics, Turner Syndrome physiopathology, White People genetics, Young Adult, Abnormalities, Multiple epidemiology, Face abnormalities, Noonan Syndrome epidemiology, Turner Syndrome epidemiology
- Abstract
Turner syndrome (TS) is a common multiple congenital anomaly syndrome resulting from complete or partial absence of the second X chromosome. In this study, we explore the phenotype of TS in diverse populations using clinical examination and facial analysis technology. Clinical data from 78 individuals and images from 108 individuals with TS from 19 different countries were analyzed. Individuals were grouped into categories of African descent (African), Asian, Latin American, Caucasian (European descent), and Middle Eastern. The most common phenotype features across all population groups were short stature (86%), cubitus valgus (76%), and low posterior hairline 70%. Two facial analysis technology experiments were conducted: TS versus general population and TS versus Noonan syndrome. Across all ethnicities, facial analysis was accurate in diagnosing TS from frontal facial images as measured by the area under the curve (AUC). An AUC of 0.903 (p < .001) was found for TS versus general population controls and 0.925 (p < .001) for TS versus individuals with Noonan syndrome. In summary, we present consistent clinical findings from global populations with TS and additionally demonstrate that facial analysis technology can accurately distinguish TS from the general population and Noonan syndrome., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)
- Published
- 2020
- Full Text
- View/download PDF
130. A Report on Ten Asia Pacific Countries on Current Status and Future Directions of the Genetic Counseling Profession: The Establishment of the Professional Society of Genetic Counselors in Asia.
- Author
-
Laurino MY, Leppig KA, Abad PJ, Cham B, Chu YWY, Kejriwal S, Lee JMH, Sternen DL, Thompson JK, Burgess MJ, Chien S, Elackatt N, Lim JY, Sura T, Faradz S, Padilla C, Paz ECD, Nauphar D, Nguyen KN, Zayts O, Vu DC, and Thong MK
- Subjects
- Asia, Education, Professional trends, Forecasting, Humans, Societies, Medical, Counselors trends, Education, Medical trends, Genetic Counseling trends, Practice Patterns, Physicians' trends
- Abstract
The Professional Society of Genetic Counselors in Asia (PSGCA) was recently established as a special interest group of the Asia Pacific Society of Human Genetics. Fostering partnerships across the globe, the PSGCA's vision is to be the lead organization that advances and mainstreams the genetic counseling profession in Asia and ensures individuals have access to genetic counseling services. Its mission is to promote quality genetic counseling services in the region by enhancing practice and curricular standards, research and continuing education. The PSGCA was formally launched during the Genetic Counseling Pre-Conference Workshop held at the 11th Asia-Pacific Conference on Human Genetics in Hanoi, Viet Nam, September 16, 2015. The pre-conference workshop provided an opportunity for medical geneticists and genetic counselors from across 10 Asia Pacific countries to learn about the varied genetic counseling practices and strategies for genetic counseling training. This paper provides an overview of the current status and challenges in these countries, and proposed course of unified actions for the future of the genetic counseling profession.
- Published
- 2018
- Full Text
- View/download PDF
131. Effects of sharing information on drug administration errors in pediatric wards: a pre-post intervention study.
- Author
-
Chua SS, Choo SM, Sulaiman CZ, Omar A, and Thong MK
- Abstract
Background and Purpose: Drug administration errors are more likely to reach the patient than other medication errors. The main aim of this study was to determine whether the sharing of information on drug administration errors among health care providers would reduce such problems., Patients and Methods: This study involved direct, undisguised observations of drug administrations in two pediatric wards of a major teaching hospital in Kuala Lumpur, Malaysia. This study consisted of two phases: Phase 1 (pre-intervention) and Phase 2 (post-intervention). Data were collected by two observers over a 40-day period in both Phase 1 and Phase 2 of the study. Both observers were pharmacy graduates: Observer 1 just completed her undergraduate pharmacy degree, whereas Observer 2 was doing her one-year internship as a provisionally registered pharmacist in the hospital under study. A drug administration error was defined as a discrepancy between the drug regimen received by the patient and that intended by the prescriber and also drug administration procedures that did not follow standard hospital policies and procedures. Results from Phase 1 of the study were analyzed, presented and discussed with the ward staff before commencement of data collection in Phase 2., Results: A total of 1,284 and 1,401 doses of drugs were administered in Phase 1 and Phase 2, respectively. The rate of drug administration errors reduced significantly from Phase 1 to Phase 2 (44.3% versus 28.6%, respectively; P <0.001). Logistic regression analysis showed that the adjusted odds of drug administration errors in Phase 1 of the study were almost three times that in Phase 2 ( P <0.001). The most common types of errors were incorrect administration technique and incorrect drug preparation. Nasogastric and intravenous routes of drug administration contributed significantly to the rate of drug administration errors., Conclusion: This study showed that sharing of the types of errors that had occurred was significantly associated with a reduction in drug administration errors., Competing Interests: Disclosure The authors report no conflicts of interest in this work.
- Published
- 2017
- Full Text
- View/download PDF
132. Sandhoff disease in two siblings of a Malaysian family: Description of novel beta hexosaminidase mutations, magnetic resonance imaging, and spectroscopic findings.
- Author
-
Antony CD, Thong MK, Rahmat K, and Muridan R
- Subjects
- Brain pathology, Humans, Infant, Male, Sandhoff Disease diagnosis, Sandhoff Disease genetics, Siblings, Magnetic Resonance Imaging methods, Mutation genetics, Sandhoff Disease pathology, beta-N-Acetylhexosaminidases genetics
- Published
- 2017
- Full Text
- View/download PDF
133. The first Malay database toward the ethnic-specific target molecular variation.
- Author
-
Halim-Fikri H, Etemad A, Abdul Latif AZ, Merican AF, Baig AA, Annuar AA, Ismail E, Salahshourifar I, Liza-Sharmini AT, Ramli M, Shah MI, Johan MF, Hassan NN, Abdul-Aziz NM, Mohd Noor NH, Nur-Shafawati AR, Hassan R, Bahar R, Zain RB, Yusoff SM, Yusoff S, Tan SG, Thong MK, Wan-Isa H, Abdullah WZ, Mohamed Z, Abdul Latiff Z, and Zilfalil BA
- Subjects
- Humans, Malaysia, Databases, Genetic, Ethnicity genetics
- Abstract
Background: The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb)., Findings: Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register )., Conclusions: This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.
- Published
- 2015
- Full Text
- View/download PDF
134. Spectrum of inherited metabolic disorders in Malaysia.
- Author
-
Thong MK and Yunus ZM
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Newborn, Malaysia epidemiology, Male, Metabolism, Inborn Errors diagnosis, Metabolism, Inborn Errors epidemiology, Metabolism, Inborn Errors therapy
- Abstract
Issues pertaining to the diagnosis and management of inborn errors of metabolism (IEM) in Malaysia included low awareness of atypical and variable presentations in IEMs leading to delayed diagnosis or treatment, absence of reliable population data on IEMs and involvement of multiple siblings in the same family due to consanguinity. The importance of careful family history taking and genetic counselling are emphasised. Selected testing of ill infants and children for IEM yielded a positive 2% (264/13,500) results for IEMs in Malaysia. Out of the 264 patients, the spectrum of IEMs in Malaysia included organic acidurias (98), aminoacidopathies (78), urea cycle defects (54), neurotransmitter conditions (12) and lysosomal disorders, mainly mucopolysaccharidosis (14). Confirmatory studies of IEMs are an important aspect of management of IEMs. There is a need for more metabolic specialists and funding for diagnosis and treatment of IEMs in Malaysia. Long-term care issues and cost-effectiveness of IEM therapy, supportive and preventive aspects will need further studies in Malaysia.
- Published
- 2008
135. Characterisation of beta-globin gene mutations in Malaysian children: a strategy for the control of beta-thalassaemia in a developing country.
- Author
-
Thong MK, Tan JA, Tan KL, and Yap SF
- Subjects
- Child, DNA genetics, Developing Countries, Gene Frequency, Genotype, Humans, Malaysia, Polymerase Chain Reaction, beta-Thalassemia diagnosis, beta-Thalassemia ethnology, Globins genetics, Mutation genetics, beta-Thalassemia genetics
- Abstract
beta-thalassaemia major, an autosomal recessive hemoglobinopathy, is one of the most common single gene disorders in multi-racial Malaysia. The control of beta-thalassaemia major requires a multi-disciplinary approach that includes population screening, genetic counselling, prenatal diagnosis and the option of termination of affected pregnancies. To achieve this objective, the molecular characterisation of the spectrum of beta-globin gene mutations in each of the affected ethnic groups is required. We studied 88 consecutive unrelated individuals and their respective families with beta-thalassaemia (74 beta-thalassaemia major, 12 HbE-beta-thalassaemia, 2 with HbE homozygotes) and four individuals with beta-thalassaemia trait that contributed a total 180 alleles for study. Using a 2-step molecular diagnostic strategy consisting of amplification refractory mutation system (ARMS) to identify the 8 most common mutations followed by other DNA-based diagnostic techniques, a total of 177 (98.3 per cent) of the 180 beta-thalassaemia alleles were characterised. One out of 91 (1 per cent) of the Chinese alleles, one out of 46 (2.2 per cent) Malay alleles and one out of two Indian alleles remained unknown. A 100 per cent success rate was achieved in studying the Kadazandusun community in this study. A strategy to identify beta-globin gene mutations in Malaysians with beta-thalassaemia is proposed based on this outcome.
- Published
- 2005
- Full Text
- View/download PDF
136. Effects of MECP2 mutation type, location and X-inactivation in modulating Rett syndrome phenotype.
- Author
-
Weaving LS, Williamson SL, Bennetts B, Davis M, Ellaway CJ, Leonard H, Thong MK, Delatycki M, Thompson EM, Laing N, and Christodoulou J
- Subjects
- Australia, Codon, Nonsense, DNA chemistry, DNA genetics, DNA Mutational Analysis, Databases as Topic, Frameshift Mutation, Genotype, Humans, Methyl-CpG-Binding Protein 2, Mutagenesis, Insertional, Mutation, Phenotype, Polymorphism, Genetic, Rett Syndrome pathology, Sequence Deletion, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins genetics, Dosage Compensation, Genetic, Repressor Proteins, Rett Syndrome genetics
- Abstract
Rett syndrome (RTT) is a clinically defined disorder that describes a subset of patients with mutations in the X-linked MECP2 gene. However, there is a high degree of variability in the clinical phenotypes produced by mutations in MECP2, even amongst classical RTT patients. In a large-scale screening project, this variability has been examined by looking at the effects of mutation type, functional domain affected and X-inactivation. Mutations have been identified in 60% of RTT patients in this study (25% of whom were atypical), including 23 novel mutations and polymorphisms. More mutations were found in classical patients (63%) compared to atypical patients (44%). All of the pathogenic mutations were de novo in patients for whom parent DNA was available for screening. A composite phenotype score was developed, based on the recommendations for reporting clinical features in RTT of an international collaborative group. This score proved useful for summarising phenotypic severity, but did not correlate with mutation type, domain affected or X-inactivation, probably due to complex interactions between all three. Other correlations suggested that truncating mutations and mutations affecting the methyl-CpG-binding domain tend to lead to a more severe phenotype. Skewed X-inactivation was found in a large proportion (43%) of our patients, particularly in those with truncating mutations and mutations affecting the MBD. It is therefore likely that X-inactivation does modulate the phenotype in RTT., (Copyright 2003 Wiley-Liss, Inc.)
- Published
- 2003
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.