Direct carrier detection by in situ suppression hybridization with cosmid clones of the Duchenne/Becker muscular dystrophy locus

A basic problem in genetic counseling of families with
Duchenne/Becker muscular dystrophy (DMD/BMD) concerns the carrier
status of female relatives of an affected male. In about 60% of
these patients, deletions of one or more exons of the dystrophin
gene can be identified. These deletions preferentially include exon
45, which can be detected by multiplex polymerase chain reaction
(PCR) and Southern blot analysis of genomic cosmid clones that map
to this critical region. As a new approach for definitive carrier
detection, we have performed chromosomal in situ suppression (CISS)
hybridization with these cosmid clones in female relatives of four
unrelated patients. In normal females, most metaphases showed
signals on both×chromosomes, whereas only one×chromosome was
labeled in carriers. Our results demonstrate that CISS
hybridization can define the carrier status in female relatives of
DMD patients exhibiting a deletion in the dystrophin gene.