title: Analysis of CTG repeat length variation in theDMPKgene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia.
abstract: The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia.
  
  
  
  We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion.
  
  
  
  The number of individuals not known to be affected by DM with (CTG)>18was determined according to ethnic group and as a whole population. The χ2test was performed to compare the distribution of (CTG)>18with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation.
  
  
  
  Of the 754 chromosomes studied, (CTG)>18frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation.
  
  
  
  The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries.
authors.affiliation: Department of Molecular Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kathlin K
authors.initials: KK
authors.lastname: Ambrose
authors.affiliation: Department of Paediatrics, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Taufik
authors.initials: T
authors.lastname: Ishak
authors.affiliation: Department of Molecular Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lay-Hoong
authors.initials: LH
authors.lastname: Lian
authors.affiliation: Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Khean-Jin
authors.initials: KJ
authors.lastname: Goh
authors.affiliation: Department of Pathology, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kum-Thong
authors.initials: KT
authors.lastname: Wong
authors.affiliation: Department of Biomedical Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Azlina
authors.initials: A
authors.lastname: Ahmad-Annuar
authors.affiliation: Department of Paediatrics, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Meow-Keong
authors.initials: MK
authors.lastname: Thong
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D015139:Blotting, Southern; D002675:Child, Preschool; D002681:China / Q000208:ethnology; D005006:Ethnicity; D005260:Female; D006801:Humans; D007194:India / Q000208:ethnology; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009223:Myotonic Dystrophy / Q000453:epidemiology / Q000235:genetics*; D065636:Myotonin-Protein Kinase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D018911:Trinucleotide Repeats / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase
keywords: CTG repeats; TP-PCR; genetic counselling; molecular diagnosis; myotonic dystrophy type 1; prevalence