Molecular analysis of 25 Chinese families with Duchenne/Becker muscular dystrophy

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked progressive neuromuscular diseases. We have collected 25 Chinese families each with at least one DMD/BMD patient for DNA analysis in the Xp21 region. Eight genomic probes, 6 within and 2 flanking the DMD gene, and 7 restriction enzymes were used to detect 9 restriction fragment length polymorphisms (RFLPs): C7-EcoRV, J-Bir-BamHI, pERT87-30-BglII, pERT87-15-BamHI, pERT87-15-XmnI, pERT87-1-XmnI, XJ1.1-TaqI, XJ5.1-SphI, and 754-PstI. From analysis of unrelated subjects, we found that the 4 most informative RFLPs in the linkage study were pERT87-15-XmnI, pERT87-1-XmnI, XJ5.1-SphI and J-Bir-BamHI. Two flanking markers, C7 and 754, were noninformative in most families. Three families (12%) had gene deletion: family M-25 at pERT87-1 to 87-30; M-105 at XJ 5.1, 1.1, pERT87-1, and 87-15; and M-110 at XJ5.1, 1.1, and pERT87-1 to 87-30. Two recombinations were detected: M-10 between C7 and pERT87-15; and M-39 between J-Bir and pERT87-15. In the 25 mothers with affected sons, 2 had gene deletion, 1 was homozygous at all 9 polymorphic loci and the other 22 were heterozygous at more than one locus. Twenty-four at-risk female siblings were studied for carriership. Nine were classified as at high risk of carriership, 13 at low risk of carriership by haplotyping, and the remaining two were uncertain, with one due to recombination and the other to maternal homozygous haplotypes. Gene deletion and RFLP analysis are very useful in genetic counseling of Chinese DMD/BMD.