Founder effect of the 669insA mutation in BSCL2 gene causing Berardinelli-Seip congenital lipodystrophy in a cluster from Brazil

Congenital generalized lipodystrophy (CGL) or Berardinelli-Seip Syndrome (BSCL) is a rare autosomal recessive disease characterized by a nearly-complete absence of adipose tissue from birth and severe metabolic alterations. The 669insA mutation in exon 4 of the BSCL2 gene was identified as the major genetic alteration leading to BSCL in a group of 22 patients from the northeastern Brazilian state of Rio Grande do Norte. Aiming to investigate the causes of the high frequency of BSCL in this region, a molecular genetic study was conducted using eight microsatelite markers located in chromosome 11. Additional investigations concerning the proportion of expected homozygous and heterozygous individuals, genetic diversity, fixation index and coefficient of endogamy were undertaken, and indicated significant differences by comparing the allelic and haplotypic frequencies observed for the BSCL affected families and the control group. It was concluded that a founder effect, genetic drift and consanguineous marriages have significantly affected the structure of this population, resulting in the highest frequency of BSCL in Brazil.