Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy

The presence of multiple affected offspring from apparently non‐carrier parents is caused by germ line mosaicism. Although germ line mosaicism has been reported for many diseases, figures for recurrence risks are known for only a few of them. In X‐linked Duchenne and Becker muscular dystrophies (DMD/BMD), the recurrence risk for non‐carrier females due to germ line mosaicism has been estimated to be between 14% and 20% (95% confidence interval 3–30) if the risk haplotype is transmitted. In this study, we have analyzed 318 DMD/BMD cases in which the detected mutation was de novo with the aim of obtaining a better estimate of the ‘true’ number of germ line mosaics and a more precise recurrence risk. This knowledge is essential for genetic counseling. Our data indicate a recurrence risk of 8.6% (4.8–12.2) if the risk haplotype is transmitted, but there is a remarkable difference between proximal (15.6%) (4.1–27.0) and distal (6.4%) (2.1–10.6) deletions. Overall, most mutations originated in the female. Deletions occur more often on the X chromosome of the maternal grandmother, whereas point mutations occur on the X chromosome of the maternal grandfather. In unhaplotyped de novo DMD/BMD families, the risk of recurrence of the mutation is 4.3%.