Riess O, Weber B, Noeremolle A, Shaikh R A, Hayden M R, Musarella M A
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Hum Mutat. 1992;1(6):478-85. doi: 10.1002/humu.1380010605.
The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.
rd小鼠的表型与人类Leber先天性黑蒙（LCA）的临床表现相似。最近，cGMP磷酸二酯酶（Pdeb）基因β亚基中的一个无义突变已被确定为小鼠rd表型的病因，并引发了关于人类PDEB基因中的突变是否可能导致LCA的问题。我们之前已经克隆并鉴定了小鼠Pdeb基因的人类同源物，并将其定位到染色体4p16.3。在本研究中，共调查了23个不同种族背景的LCA家系。使用高度多态性的（CA）n微卫星进行连锁分析，已排除PDEB基因是6个家系中LCA的病因。在其余17个家系中，我们使用单链凝胶电泳（SSGE）在PDEB基因的22个外显子中寻找突变。已确定多个外显子多态性。然而，在我们的研究人群中未发现PDEB基因中有可导致LCA表型的DNA变化。
