Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by rapidly progressive muscle weakness. The disease is caused by deletion, duplication or point mutation of the dystrophin gene, located on the X chromosome (Xp21). Deletion accounts for 60% of the mutations within the 79 exons of the dystrophin gene. Seven exons (43, 44, 45, 46, 49, 50, and 51) were found to be most commonly deleted among the Asian patients. To detect the frequency of deletion of these 7 exons in Malaysian DMD patients, we carried out a molecular genetic analysis in 20 Malaysian DMD patients. The mean age of initial presentation was 60 months (SD 32 months, range 5-120 months). Fourteen patients were found to have deletion of at least one of the seven exons. The remaining six patients did not show any deletion on the tested exons. Deletions of exons 49, 50 and 51 were the most frequent (71.43%) and appear to be the hot spots in our cohort of patients.
In Duchenne muscular dystrophy (DMD), identification of one nonsense mutation in the DMD gene has been considered an endpoint of genetic diagnosis. Here, we identified two closely spaced nonsense mutations in the DMD gene. In a Malaysian DMD patient two nonsense mutations (p.234S>X and p.249Q>X, respectively) were identified within exon 8. The proband's mother carried both mutations on one allele. Multiple mutations may explain the occasional discrepancies between genotype and phenotype in dystrophinopathy.
Clinical data on Duchenne muscular dystrophy (DMD) are lacking in developing countries. The objective of this study was to delineate the demographic characteristics, investigations, and outcome of 21 Malaysian males diagnosed with DMD over a period of 10 years. Mean age presentation was 3 years 8 months (SD 23mo; range 10 to 84mo), mean duration from first presentation to diagnosis was 3y 7mo (SD 26mo; range 5 to 84) and the mean age for loss of ambulation was 11 years (SD 25mo; range 102 to 168). There was family history of DMD in five of the 21 patients. Muscle biopsy showed confirmatory findings of DMD in the 16 patients tested. Molecular genetic analysis showed dystrophin gene deletions in 11 of these 16 patients. Four and seven of the students stopped schooling and had learning difficulties, respectively; only nine had satisfactory school performances. Eight out of 14 patients evaluated were classified as having severe to total dependency levels on the modified Barthel Index for activities of daily living assessment. DMD is associated with significant medical and social needs for a developing country such as Malaysia. Earlier referral, genetic counselling, and provision of support and rehabilitative services are the main priorities.
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.