DNA analysis of Duchenne and Becker muscular dystrophy using pERT87 genomic probes and dystrophin cDNA probes--establishing the optimum strategy for carrier diagnosis in the Japanese population.

DNA analysis was performed on 19 unrelated Duchenne muscular dystrophy (DMD) families and one Becker muscular dystrophy (BMD) family in Japan to determine their carrier status. The intragenic genomic probe pERT87 with its subclones 87-1, 87-8, and 87-15 were used together with five cDNA probes from the 5' end of the dystrophin gene. The tests with both a high polymorphism information content (P.I.C.) and a high observed P.I.C. were most effective, i.e., pERT87-1/XmnI, pERT87-15/XmnI, pERT87-8/TaqI, and pERT87-8/BstXI. These test combinations were useful in the Japanese population but pERT87-15/TaqI was not, although it was effective in Caucasians. Two additional test combinations of pERT87-1/MspI and pERT87-15/BamHI were highly useful in detecting restriction fragment length polymorphisms (RFLPs) when other tests were not informative. Carrier status could be determined in 18 out of 20 clients who were at risk for DMD/BMD carrier status from 20 families, similar to the rate of detection in Caucasians. The total detection rate of deletions was 74% with the five cDNA probes. Deletions were concentrated on two hot spots where 92% of all deletions were detected by only two probes, 1-2a and 8. Deletions were detected in two males with DMD who had none of the eight RFLPs tested. Our results emphasize the usefulness of DNA analysis with pERT87 genomic probes and cDNA probes. In addition, an optimum strategy for carrier detection in Japanese DMD/BMD families was proposed.