Fabry disease: Evidence for a regional founder effect of the gene mutation 30delG in Brazilian patients.

The Fabry disease is caused by mutations in the gene () that encodes the enzyme α-galactosidase A (α-Gal A). More than 500 pathologic variants of have already been described, most of them are family-specific. In southern Brazil, a frequent single-base deletion ( 30delG) was identified among four families that do not recognize any common ancestral. In order to investigate the history of this mutation (investigate the founder effect, estimate the mutation age and the most likely source), six gene-flanking microsatellite markers of the X chromosome on the mutation carriers and their parents, 150 individuals from the same population and 300 individuals that compose the Brazilian parental populations (Europeans, Africans and Native Americans) were genotyped. A common haplotype to the four families was identified and characterized as founder. The age was estimated with two statistics software (DMLE 2.2 and ESTIAGE) that agreed with 11 to 12 generations old. This result indicates that the mutation 30delG was originated from a single event on the X chromosome of a European immigrant, during the southern Brazil colonization between 1710 and 1740.