Theoretical expectations for deletional mutations in Duchenne muscular dystrophy

✍ Scribed by Giannelli, Francesco ;Opitz, John M.

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 89 KB
• Volume: 31
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320310435

✦ Synopsis

The letter by on the theoretical expectations for deletional mutations in Duchenne muscular dystrophy (DMD) is very misleading. The authors base al1 of their arguments and calculations on the hypothesis that, in DMD, deletions occur exclusively or aimost exclusively by homologous recombination, and hence, at female meiosis. There is no evidence for such a hypothesis. Sequence analysis of deletion junctions in mutations or different genes shows that deletions may occur both by homologous and nonhomologous or "illegitimate" recombination, and that the latter are probably more frequent Anderson, 19871. The ways in which deletions by illegitimate recombination may occur are uncertain, but it is reasonable to assume that they largely happen at DNA replication [Green et al., 19881. Since male germ cells undergo a much greater number of DNA replications, deletions by illegitimate recombination could be more frequent in male gametes. The occurrence of two carriers of DMD deletions among the offspring of normal homozygous mothers Lanman et al., 19871 may support the idea that deletions at the DMD locus frequently occur during germ cell proliferation so as to lead to gonadal mosaicism.