DNA polymorphisms and deletion analysis of the Duchenne-Becker muscular dystrophy gene in the Chinese

In our investigation of Duchenne muscular dystrophy (DMD)-Becker muscular dystrophy (BMD) gene in the Chinese, the analysis of relevant restriction fragment length polymorphisms (RFLPs) was first made in 30 normal female volunteers to determine their allele and genotype frequencies, and then in 29 DMD-BMD families for informativeness of different combinations of RFLPs in making carrier detection and prenatal diagnosis. We further screened the mutant gene, first with four 5' end intronic, genomic probes (pERT87-1, pERT87-8, pERT87-15, and XJ1.1) which did not show any deletions, and then with all dystrophin cDNA probes which disclosed 13 partial gene deletions out of 29 patients studied (45%). The deletions were nonrandomly distributed, clustering primarily near the central region of the gene. Fifty percent of the deletions involved single exon-containing HindIII restriction fragments, and again most were located near the center of the gene, emphasizing the importance of this area. Some exceptions were found against the previous suggestion that intactness of translational open reading frame resulted in a BMD phenotype. Neither the location of the breakpoints nor the length of the deletions was useful in predicting a certain phenotype. One of our patients had an intriguing pattern of partial gene deletion that lost part of the gene at the 3' end. Carrier determination was attempted by use of dosage analyses or identification of junction fragments which greatly improved accuracy and reliability.