Genome-wide linkage scan for bladder exstrophy-epispadias complex.
BACKGROUND
The bladder exstrophy-epispadias complex represents 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. Previous studies are suggestive of an underlying multifactorial mode of inheritance. However, no genetic or nongenetic factor has been identified so far. In this study, we sought risk loci by parametric and nonparametric linkage analysis, searching for homozygous segments, and more complex inherited loci, respectively.


METHODS
Two pedigrees, Spanish and German, each comprising two members affected with classical bladder exstrophy, were analyzed by genome-wide linkage scan.


RESULTS
Evidence for possible risk/modifying loci on chromosomes 2p22.1-p21, 2p25.2-p25.1, 4q23-q32.3, 7q21.3-q33, 7q34-q36.1, 14q31.1-q32.2, and 19q13.33-q13.43 (LOD scores >1.50) was obtained.


CONCLUSIONS
This study was the first positional approach to identify chromosomal candidate regions causally related to bladder exstrophy-epispadias complex. Our results suggest the presence of susceptibility genes in the regions identified. These regions need to be confirmed in future studies.
Ludwig
Michael
M
Department of Clinical Biochemistry and Pharmacology, University of Bonn, Sigmund-Freud-Strasse 25, Bonn. mludwig@uni-bonn.de
Rüschendorf
Franz
F
Saar
Kathrin
K
Hübner
Norbert
N
Siekmann
Lothar
L
Boyadjiev
Simeon A
SA
Reutter
Heiko
H
D000015:Abnormalities, Multiple / Q000235:genetics; D001746:Bladder Exstrophy / Q000150:complications / Q000235:genetics*; D002874:Chromosome Mapping; D004842:Epispadias / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide