Genomic analysis of Brazilian patients with Fabry disease

Abstract

Fabry disease is an X-linked lysosomal disorder due to α-galactosidase A deficiency that causes storage of globotriaosylceramide. The gene coding for this lysosomal enzyme is located on the long arm of the X chromosome, in region Xq21.33-Xq22. Disease progression leads to vascular disease secondary to involvement of kidney, heart and the central nervous system. Detection of female carriers based solely on enzyme assays is often inconclusive. Therefore, mutation analysis is a valuable tool for diagnosis and genetic counseling. Many mutations of the α-galactosidase A gene have been reported with high genetic heterogeneity, being most mutations private found in only one family. The disease is panethnic, and estimates of incidence range from about 1 in 40,000 to 60,000 males. Our objective was to describe the analysis of 6 male and 7 female individuals belonging to 4 different Fabry disease families by automated sequencing of the seven exons of the α-galactosidase gene. Sequencing was performed using PCR fragments for each exon amplified from DNA extracted from peripheral blood. Three known mutations and one previously described in another Brazilian family were detected. Of 7 female relatives studied, 4 were carriers. Although the present study confirms the heterogeneity of mutations in Fabry disease, the finding of the same mutation previously detected in another Fabry family from our region raises the possibility of some founder effect, or genetic drift. Finally, the present study highlights the importance of molecular analysis for carrier detection and genetic counseling.

New mutations in the GLA gene in Brazilian families with Fabry disease

“…In this study the authors described four mutations (30delG, 1033delTC, W349X and L36F). 42 Therefore, our data show the analysis of a much higher number of FD individuals and families. The data show the extensive molecular genetics heterogeneity in this disease and support the fact that many of the GLA mutations causing FD are familyspecific.…”

Identification of mutations in Colombian patients affected with Fabry disease

“…When comparing the mutations present in the Colombian population with the mutation profile identified in other Latin American countries (Argentina, Mexico and Brazil) (Politei et al, 2013;Ramos-Kuri et al, 2014;Rozenfeld et al, 2006) and Spain (Pereira et al, 2007;Turaça et al, 2012;Rodríguez-Marí et al, 2003) no association is found. This is probably a consequence of the limited sample size analyzed in most of the previous studies that evaluate the mutation profile, such as Argentinean and Mexican studies.…”

Kidney Function and 24-Hour Proteinuria in Patients with Fabry Disease during 36 Months of Agalsidase Alfa Enzyme Replacement Therapy: A Brazilian Experience

“…[2] There were no cases of hypertensive disorder, smoking, hyperlipidemia, or other chronic diseases. Neurologic and molecular characteristics of this population have already been published [20][21][22][23] and are summarized in Table 1.…”