Analysis of CTG repeat length variation in the gene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia.

Objective: 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.

Design, Setting And Participants: 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.

Outcome Measures: The number of individuals not known to be affected by DM with (CTG) was determined according to ethnic group and as a whole population. The χ test was performed to compare the distribution of (CTG) with 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.

Results: Of the 754 chromosomes studied, (CTG) frequency 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.

Conclusions: 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.