Background: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of anomalies involving the abdominal wall, pelvis, urinary tract, genitalia, and, occasionally, the spine and anus. Although BEEC typically occurs sporadically, families with two or more affected members have been reported. The present authors previously conducted a genome-wide linkage analysis in two multiply affected (multiplex) families (one of German and one of Spanish origin), which revealed several chromosomal regions compatible with linkage. In the present study, genome-wide linkage analysis was performed in a recently reported consanguineous Iranian multiplex family with an affected sibling pair: a female with epispadias and a male with classic exstrophy of the bladder.
Methods: The Affymetrix 250K Sty chip (238,304 single nucleotide polymorphisms) was used to genotype the parents and four children, including the two affected siblings. Parametric and nonparametric linkage analyses were performed.
Results: Parametric linkage analysis under a recessive model with complete penetrance identified seven loci with LOD scores >1.6 (1p33, 4q31.21-22, 9q22.33, 12q13.13-2, 13q12.12-13, 18q23, and 19q13.31-41). These results were supported by nonparametric linkage analysis. Haplotype analysis showed that the affected individuals were homozygous identical by descent for all seven regions. Two of these regions overlapped with regions observed previously in the Spanish family -one on chromosome 4q31.21-22, and the other on chromosome 19q13.31-41.
Conclusion: These results suggest that chromosomal regions 4q31.21-22 and 19q13.31-41 are likely to harbor genes for an autosomal recessive form of BEEC.
© 2010 Wiley-Liss, Inc.