Maternal germline mosaicism in Fabry disease

Fabry disease (FD) is an X-linked monogenic disorder caused by mutations in the GLA gene which leads to a deficiency of the functionally active lysosomal α-galactosidase A enzyme. Here, we report on a family of five members: unaffected parents, one unaffected son, and another son and daughter both carrying the same mutation (p.G138E) in the GLA gene. Genotype analysis using intragenic GLA markers confirmed the maternal origin of the mutation. The affected son and daughter carried the same mutation; however, it was not detected in the peripheral blood, buccal cells, and urinary sediment cells of their mother. Moreover, the unaffected son without the alteration in the GLA gene carried the same maternal chromosome X (disease-associated) haplotype. To the best of our knowledge, this study represents the first case of maternal germline mosaicism in FD.