Reassessing carrier status for dystrophinopathies

The cloning of the gene, and the identifications of mutations in it as the cause of Duchenne muscular dystrophy (DMD), makes a compelling story that is aptly told elsewhere. The locus-the largest in the human genome-consists of 79 exons, distributed over 2.5 million nucleotides on the X chromosome, which are assembled into a complementary DNA (cDNA) of around 14 kb encoding the predominant muscle isoform of the dystrophin protein. The size of the gene, and the number of exons, had historically made mutation analysis challenging. For more than a decade, the standard clinical assay was a multiplex PCR test that amplified sequences from a limited number of exons; nevertheless, because it included exons within the deletion hotspots of the gene, this method could confirm the presence of mutations in up to 98% of boys with exonic deletions. .