Ludwig Michael, Rüschendorf Franz, Saar Kathrin, Hübner Norbert, Siekmann Lothar, Boyadjiev Simeon A, Reutter Heiko
Department of Clinical Biochemistry and Pharmacology, University of Bonn, Sigmund-Freud-Strasse 25, Bonn.
Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):174-8. doi: 10.1002/bdra.20512.
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.
Two pedigrees, Spanish and German, each comprising two members affected with classical bladder exstrophy, were analyzed by genome-wide linkage scan.
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.
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.
膀胱外翻-尿道上裂复合畸形代表了一系列泌尿生殖系统异常，其中部分或全部远端尿路未能闭合并暴露于腹壁外。先前的研究提示其存在潜在的多因素遗传模式。然而，迄今为止尚未确定任何遗传或非遗传因素。在本研究中，我们分别通过参数化和非参数化连锁分析寻找风险基因座，搜索纯合片段以及更复杂的遗传基因座。
对两个家系，即西班牙家系和德国家系进行全基因组连锁扫描分析，每个家系均包含两名患有典型膀胱外翻的成员。
在染色体2p22.1-p21、2p25.2-p25.1、4q23-q32.3、7q21.3-q33、7q34-q36.1、14q31.1-q32.2和19q13.33-q13.43上获得了可能的风险/修饰基因座的证据（对数优势分数>1.50）。
本研究是首次通过定位方法来识别与膀胱外翻-尿道上裂复合畸形因果相关的染色体候选区域。我们的结果提示在已确定的区域中存在易感基因。这些区域需要在未来的研究中得到证实。
