A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene
A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene
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DOI：
10.1086/302101
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发表时间：
1998-11-01
影响因子：
9.8
通讯作者：
Daiger, SP
中科院分区：
文献类型：
--
作者：
Sohocki, MM;Sullivan, LS;Daiger, SP
视网膜表达基因 CRX（视锥杆同源框基因）的突变与显性视锥杆营养不良和新发莱伯先天性黑蒙有关。然而，CRX 是多个视网膜基因的转录因子，包括视蛋白和光感受器间视黄醇结合蛋白的基因。由于 CRX 功能的丧失可能会改变许多其他视网膜蛋白的表达，因此我们在患有一系列退行性视网膜疾病的先证者中筛选了 CRX 基因的突变。在筛选的 294 名无关个体中，我们在临床诊断常染色体显性锥杆营养不良、晚发性显性视网膜色素变性或显性先天性莱伯黑蒙（早发性色素性视网膜炎）的家族中发现了 4 种 CRX 突变，并且我们还发现了另外 4 种良性序列变异。这些发现表明，CRX 突变可能与多种临床表型相关，包括先天性视网膜营养不良 (Leber) 和发病范围广泛的进行性疾病，如视锥杆营养不良或色素性视网膜炎。
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.