Sohocki M M, Sullivan L S, Mintz-Hittner H A, Birch D, Heckenlively J R, Freund C L, McInnes R R, Daiger S P
Human Genetics Center, School of Public Health, The University of Texas Health Science Center, Houston, TX 77225-0334, USA.
Am J Hum Genet. 1998 Nov;63(5):1307-15. doi: 10.1086/302101.
Mutations in the retinal-expressed gene CRX (cone-rod homeobox gene) have been associated with dominant cone-rod dystrophy and with de novo Leber congenital amaurosis. However, CRX is a transcription factor for several retinal genes, including the opsins and the gene for interphotoreceptor retinoid binding protein. Because loss of CRX function could alter the expression of a number of other retinal proteins, we screened for mutations in the CRX gene in probands with a range of degenerative retinal diseases. Of the 294 unrelated individuals screened, we identified four CRX mutations in families with clinical diagnoses of autosomal dominant cone-rod dystrophy, late-onset dominant retinitis pigmentosa, or dominant congenital Leber amaurosis (early-onset retinitis pigmentosa), and we identified four additional benign sequence variants. These findings imply that CRX mutations may be associated with a wide range of clinical phenotypes, including congenital retinal dystrophy (Leber) and progressive diseases such as cone-rod dystrophy or retinitis pigmentosa, with a wide range of onset.
视网膜表达基因CRX（视锥-视杆同源盒基因）的突变与显性视锥-视杆营养不良以及新发的莱伯先天性黑矇有关。然而，CRX是包括视蛋白和光感受器间类视黄醇结合蛋白基因在内的多个视网膜基因的转录因子。由于CRX功能丧失可能会改变许多其他视网膜蛋白的表达，我们在一系列退行性视网膜疾病的先证者中筛查了CRX基因的突变。在筛查的294名无亲缘关系的个体中，我们在临床诊断为常染色体显性视锥-视杆营养不良、迟发性显性视网膜色素变性或显性先天性莱伯黑矇（早发性视网膜色素变性）的家族中鉴定出4个CRX突变，另外还鉴定出4个良性序列变异。这些发现表明，CRX突变可能与多种临床表型有关，包括先天性视网膜营养不良（莱伯）以及进行性疾病，如视锥-视杆营养不良或视网膜色素变性，且发病范围广泛。
