The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

Abstract

Background/Aim. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. They are X-linked recessive diseases, where males are affected and females are mostly healthy carriers of the mutation. It is estimated that 2/3 mothers of DMD probands are carriers, while 1/3 of patients have de novo mutations. The aim was to confirm the carrier status of females in the families of DMD/BMD probands, using direct genetic methods. Methods. We tested 38 females from 31 families of DMD/BMD probands with deletion/duplication in the dystrophin gene. Also, 4 cases of prenatal diagnosis of DMD/BMD were included. We preformed the polymerase chain reaction (PCR) and the multiplex ligation-dependent method (MLPA) for deletion detection, i.e. deletion/duplication in the dystrophin gene. Results. In 31 DMD/BMD probands, we identified 87.1% deletions and 12.9% duplications of one or more exons. Of the 29 tested mothers, mutations were found in 17 (14 deletions and 3 duplications). Mutations were found in 57.9% (11/19) mothers of DMD and in 60% (6/10) mothers of BMD, respectively. Also, in probands with deletions 56% (14/25) of mothers were carries and in probands with duplications 3 mothers of 4 (75%). Of the 9 other female relatives, mutations were found in 4. In prenatal diagnosis, we identified deletion in one male and one female foetus of one mother. Conclusion. The study showed that mothers were carriers in almost 60% of sporadic cases of DMD/BMD with deletions and duplication. Also, the carrier frequency tended to be higher in mothers of the probands with duplication (75%) then in probands with deletions (56%). In the case of a mother who was confirmed as a carrier, deletion was detected in 2 of 3 foetuses.