Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa
Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa
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DOI：
10.1086/518426
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发表时间：
2007-07-01
影响因子：
9.8
通讯作者：
De Baere, Elfride
中科院分区：
文献类型：
--
作者：
Coppieters, Frauke;Leroy, Bart P.;De Baere, Elfride
常染色体显性遗传性视网膜色素变性是一组遗传异质性的视网膜营养不良，其中54%的病例可归因于17个疾病位点。在这里，我们描述了光感受器细胞特异性核受体基因NR2E3的定位和鉴定，它是一种新的ADRP的致病基因和基因。在一个患有adrp的比利时大家族中，在NR2E3的第一个锌指上发现了一个杂合突变c.166G->；A(p.Gly56Arg)。总体而言，在87个潜在显性视网膜营养不良的无关家系中，该错义突变在3个受ADRP影响的家系中被发现(3.4%)，其中47个受rp影响(6.4%)。有趣的是，这些家族中受影响的成员表现出一种新的可识别的与NR2E3相关的ADRP临床亚型。此前已经证明，NR2E3的其他突变会导致常染色体隐性遗传增强型S视锥综合征，这是一种特殊的视网膜表型。我们对这些不同的显性和隐性表型提出了不同的致病机制，这可能归因于NR2E3在视杆发育和维持过程中对光感受器特异基因的双重关键调控作用。
Autosomal dominant retinitis pigmentosa" (adRP) refers to a genetically heterogeneous group of retinal dystrophies, in which 54% of all cases can be attributed to 17 disease loci. Here, we describe the localization and identification of the photoreceptor cell-specific nuclear receptor gene NR2E3 as a novel disease locus and gene for adRP. A heterozygous mutation c. 166G -> A (p. Gly56Arg) was identified in the first zinc finger of NR2E3 in a large Belgian family affected with adRP. Overall, this missense mutation was found in 3 families affected with adRP among 87 unrelated families with potentially dominant retinal dystrophies ( 3.4%), of which 47 were affected with RP ( 6.4%). Interestingly, affected members of these families display a novel recognizable NR2E3-related clinical subtype of adRP. Other mutations of NR2E3 have previously been shown to cause autosomal recessive enhanced S-cone syndrome, a specific retinal phenotype. We propose a different pathogenetic mechanism for these distinct dominant and recessive phenotypes, which may be attributed to the dual key role of NR2E3 in the regulation of photoreceptor-specific genes during rod development and maintenance.