Genome-Wide Linkage Scan in a Moroccan Family With Autosomal-Recessive Exstrophy of the Bladder Identifies a Novel Susceptibility Locus on Chromosome 3p25.3
Purpose Exstrophy of the bladder (EB) is part of the bladder exstrophy-epispadias complex (BEEC) representing a spectrum of urogenital anomalies in which part or all of the distal urinary tract fail to close and are exposed on the outer abdominal wall. Familial occurrence is rare and previous studies are suggestive of an underlying multifactorial mode of inheritance. However, no causally related genetic or non-genetic factor has been identified so far. In this study, we aim to identify potential risk/modifying loci that might contribute to EB. Material and Methods A genome-wide linkage scan was performed in a consanguineous kindred of Moroccan origin where three affected males showed the same phenotype of classic EB. Results Strongest evidence for linkage was obtained for chromosomal region 3p25.3 (parametric LOD score of 3.4). This region comprises at least seven genes listed in the current NCBI map (Build 36.1) and sequence analysis of all these genes has been initiated. Conclusions Our data provide a basis for the localization and identification of a causally related gene implicated in EB, most likely localized on 3p25.3.