AB032. Mutation spectrum in the dystrophin gene disclosed by multiplex ligation-dependent probe amplification in 181 Vietnamese Duchenne/Becker muscular dystrophy patients

Abstract: Duchenne/Becker muscular dystrophy (DMD/BMD) the most common X-linked muscular dystrophy is caused by mutation in dystrophin gene. Deletion and duplication in the dystrophin gene account for 60-70% of mutation. Multiplex ligation-dependent probe amplification (MLPA) is the most powerful and convenient method to identify exon deletions or duplications in the dystrophin gene because of its overall gene coverage. The present investigation was designed to detect mutation in the dystrophin gene in 181 unrelated Vietnamese Becker/Duchenne patients using MLPA analysis. Among the 181 cases, deletions and duplications encompassing one or more exons were identified in 105 (58%) or 12 (6.6%) cases, respectively. Deletions were found to cluster in the proximal (14.3%) and central hotspot regions (72.4%); 14% were observed to have gross deletions and 1.2% had deletion out of hotspot regions (exon 61-67). The deletion patterns were categorized into 48 patterns. Deletion of exon 48-50 or 45-50 where the most common pattern was deletion of exon 48-50, which was found in 11 cases (10%). Single-exon deletion was found in 14 cases (13%) by MLPA. Further examination disclosed that one of them was not an exon deletion but a single-nucleotide change (c.2227C > T) leading to a nonsense mutation. Outliers from the reading frame rule were 11 DMD (10.4%). Remarkably, 25 and 14 cases were found treatable by exon 51 and 53 skipping, respectively. From these findings, the largest mutation database of Vietnam dystrophinopathy was established.

Keywords: Duchenne/Becker muscular dystrophy (DMD/BMD); dystrophin; multiplex ligation-dependent probe amplification (MLPA); deletion; duplication