Detection of germline mosaicism in two Duchenne muscular dystrophy families using polymorphic dinucleotide (CA)n repeat loci within the dystrophin gene.

Background: Approximately one-third of new cases of Duchenne muscular dystrophy (DMD) can be attributed to sporadically arising new mutations, however in the majority of cases the DMD mutation has been inherited from the mother. These female carriers can have either a constitutive or mosaic mutation.

Aim: The aim of this study was to determine the segregation of the at-risk haplotype and to find a deletion in the dystrophin gene of patients.

Method: We analyzed individuals from two families with a history of DMD in order to predict the carrier status of related females. In one of these cases the mother had two affected sons, while in the other one son and two grandchildren were affected; therefore we predict that the mother would be an obligatory carrier.

Results: Haplotype analysis of the DMD loci revealed that in the two families both the healthy and affected brothers had inherited the same X maternal chromosome. However, the affected brother carried a deletion, which was absent in the unaffected sibling.

Conclusion: These findings suggested that the mothers in the two families were germline mosaics for the DMD gene. The results of this study demonstrate the usefulness of the methodology that combine the haplotype analysis with the identification of the mutation in order to detect hidden germline mosaicisms and, thus, improve genetic counseling.