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Abstract
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)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 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)>18 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.
- CTG repeats
- genetic counselling
- myotonic dystrophy type 1
- molecular diagnosis
- TP-PCR
- prevalence
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Footnotes
KKA, TI and M-KT contributed equally to the manuscript.
Contributors All authors were involved in the conception and design of the work as well as the final approval of the submitted manuscript. KKA and TI were involved in the acquisition and analysis of data and KKA, TI and M-KT were involved in the drafting of the manuscript. LHL, KJG, KTW, AA-A and M-KT contributed to the critical evaluation of the manuscript.
Funding This study was supported by grants from the Ministry of Higher Education, Malaysia (Fundamental Research Grant Scheme; grant number: FG029/2010A), University of Malaya (Postgraduate Research Fund; grant number: PV126/2012A, UM HIR grant number UM.C / 625 / 1 / HIR / MOHE / MED / 27), research grant from the Malaysian Rare Disorders Society and Page Charge Fund from the Institute of Research Management and Monitoring, University of Malaya.
Competing interests None declared.
Ethics approval Ethical approval to conduct this study was obtained from the University of Malaya Medical Centre (UMMC) Ethics Committee (reference numbers 577.17 and 800.6).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.