Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis
Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis
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DOI：
10.1073/pnas.95.6.3088
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发表时间：
1998-03-17
影响因子：
11.1
通讯作者：
Dryja, TP
中科院分区：
文献类型：
--
作者：
Morimura, H;Fishman, GA;Dryja, TP
RPE65是一种由视网膜色素上皮特异性表达的功能未知的蛋白质。我们在 147 名无关的常染色体隐性视网膜色素变性 (RP) 患者、15 名分离性 RP 患者和 45 名莱伯先天性黑蒙 (LCA) 患者中检查了该基因的所有 14 个外显子。在两名隐性 RP 患者、一名分离 RP 重新归类为隐性的患者以及七名 LCA 患者中发现了可能致病的序列异常。每个可用家族中的共分离分析表明，所有受影响的个体要么是纯合子，要么是复合杂合子，所有未受影响的个体要么是杂合子携带者，要么是纯合野生型。在一个家族中，受影响个体的任一亲本中都不存在一个新突变的实例。在另一个家族中，在三个分支（即三对不同的亲本）中具有隐性RP的受影响成员是相同两个突变的复合杂合子或其中一个突变的纯合子，根据我们的结果，RPE65 基因突变似乎约占隐性 RP 病例的 2%，约占 LCA 病例的 1.6%。
RPE65 is a protein of unknown function expressed specifically by the retinal pigment epithelium. We examined all 14 exons of this gene in 147 unrelated patients with autosomal recessive retinitis pigmentosa (RP), in 15 patients with isolate RP, and in 45 patients with Leber congenital amaurosis (LCA). Sequence anomalies that were likely to be pathogenic were found in two patients with recessive RP, in one patient with isolate RP recategorized as recessive, and in seven patients with LCA. Cosegregation analysis in each available family showed that all affected individuals were either homozygotes or compound heterozygotes and that all unaffected individuals were either heterozygote carriers or homozygous wild type, In one family, there was one instance of a new mutation not present in either parent of the affected individual, In another family, affected members with recessive RP in three branches (i.e., three distinct pairs of parents) were compound heterozygotes for the same two mutations or homozygous for one of them, Based on our results, mutations in the RPE65 gene appear to account for approximate to 2% of cases of recessive RP and approximate to 1.6% of cases of LCA.