Abstract
BackgroundDNA deletion and duplication were determined as the major mutation underlying Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).MethodApplying multiplex ligation-dependent probe amplification (MLPA), we have analyzed 179 unrelated DMD/BMD subjects from northern China.ResultsSeventy-three percent of the subjects were found having a deletion (66.25%) or duplication (6.25%). Exons 51–52 were detected as the most common fragment deleted in single-exon deletion, and the region of exons 45–50 was the most common exons deleted in multi-exon deletions. About 90% of DMD/BMD cases carry a small size deletion that involves 10 exons or less, 26.67% of which carry a single-exon deletion. Most of the smaller deletions resulted in an out-of-frame mutation. The most common exons deleted were determined to be between exon 48 and exon 52, with exon 50 was the model allele. Verifying single-exon deletion, one sample with a deletion of exon 53 that was initially observed from MLPA showed that there was a single base deletion that abolished the ligation site in MLPA. Confirmation of single-exon deletion is recommended to exclude single base deletion or mutation at the MLPA ligation site.ConclusionThe frequency of deletion and duplication in northern China is similar to global ethnic populations.
Highlights
DNA deletion and duplication were determined as the major mutation underlying Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD)
The dystrophin gene consists of 79 exons and encodes a 14.6 kb mRNA, which is expressed in skeleton, muscles and
multiplex ligation-dependent probe amplification (MLPA) should be considered as the initial test for the clinically suspected DMD/BMD patients as well as for women who have a DMD/BMD family history, as suggested previously [29], to provide both confirmation of genetic defects on DMD gene and better genetic counseling
Summary
DNA deletion and duplication were determined as the major mutation underlying Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). 1/18,000 in male living births, respectively [3,4] They both are caused by genetic defects of the dystrophin gene, which is located at Xq21.2, spanning 2.4 Mb [5,6]. Duplications and point mutations have been reported in most exons of this gene. Mutations affecting open-reading frame (ORF), due to a frameshift, may result in an aberrantly spliced mRNA and generate a truncated, nonfunctional dystrophin protein that usually gives rise to the DMD/BMD phenotypes. About 65% of cases are caused by deletion [8,9,13], approximately 5% by duplication [9,14] and the remaining is point mutation of the dystrophin gene [15]. The frequency of complex rearrangement was reported as high as 4% [17], usually complex rearrangement is considered as a rare condition [18,19,20] that includes double deletion [17] and non-contiguous duplications [21,22,23]
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