Mutation Spectrum of Dystrophin Gene in Malaysian Patients with Duchenne/Becker Muscular Dystrophy

Abstract

We undertook the clinical feature examination and dystrophin analysis using multiplex ligation-dependent probe amplification (MLPA) and direct DNA sequencing of selected exons in a cohort of 35 Malaysian Duchenne/Becker muscular dystrophy (DMD/BMD) patients. We found 27 patients with deletions of one or more exons, 2 patients with one exon duplication, 2 patients with nucleotide deletion, and 4 patients with nonsense mutations (including 1 patient with two nonsense mutations in the same exon). Although most cases showed compliance to the reading frame rule, we found two unrelated DMD patients with an in-frame deletion of the gene. Two novel mutations have been detected in the Dystrophin gene and our results were compatible with other studies where the majority of the mutations (62.8%) are located in the distal hotspot. However, the frequency of the mutations in our patient varied as compared with those found in other populations.

Keywords::

• Becker muscular dystrophy
• DNA sequencing
• Duchenne muscular dystrophy
• dystrophin
• MLPA

ACKNOWLEDGMENTS

We would like to thank the clinicians, patients, and patients’ families for their cooperation in this study. We also express our sincerest gratitude to Assoc. Prof. Dr. Zafarina Zainuddin of USM School of Health Sciences for her help and support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by Research University Grants 1001/PPSP/812058, 1001/PPSP/812048, and 1001/PPSP/812072 from Universiti Sains Malaysia. Rani A. Qawee is the recipient of the Universiti Sains Malaysia Fellowship for Doctoral course.