Screening for DMD/BMD deletion carriers by fluorescence in situ hybridization

Fluorescence in situ hybridization (FISH) serves as an excellent alternative for direct detection of heterozygous deletions. Using a set of exon-specific cosmid DNA probes representing 18 exons, one-color FISH on metaphase and interphase preparations was performed to identify Duchenne/Becker muscular dystrophy (DMD/BMD) deletion carriers. The peripheral blood samples from 9 normal male or female controls and 5 females of independent DMD/BMD families, as well as 2 amniotic fluid specimens and 2 chorionic villus samples (CVS) from normal pregnant females, were analyzed. Expected signals were displayed in 72-100% of peripheral blood lymphocyte metaphases or interphases, 60-70% of amniocyte interphases, and 95-99% of chorionic villus cell interphases. One suspected female was identified as a deletion carrier and two were excluded. The results indicated that metaphase and interphase FISH were both useful for detection of heterozygous deletions. FISH, in combination with other available techniques, allowed efficient screening of DMD/BMD deletion carriers. The study also offered preliminary results in support of an approach to prenatal diagnosis of potential fetal carriers.