Two distinct kerato-epithelin mutations in Reis-Bucklers corneal dystrophy
Two distinct kerato-epithelin mutations in Reis-Bucklers corneal dystrophy
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DOI：
10.1016/s0002-9394(98)00135-4
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发表时间：
1998-10-01
影响因子：
4.2
通讯作者：
Tano, Y
中科院分区：
文献类型：
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作者：
Okada, M;Yamamoto, S;Tano, Y
目的：两例患者被诊断为Reis-Bucklers角膜营养不良（RBCD），尽管角膜混浊的模式和严重程度不同。为了了解这些表型变异是否存在遗传基础，我们分析了β ig-h3基因，该基因编码角质上皮蛋白，并包含导致RBCD的突变（Arg555Gln）。方法：一名30岁男性中央角膜出现蜂窝状上皮下混浊，一名25岁男性出现进行性上皮下地理混浊，均被认为患有RBCD。我们从两名患者及其家庭成员的白细胞中分离基因组DNA，筛选Arg555Gln角上皮突变。然后，我们使用单链构象多态性（SSCP）技术分析该基因的所有外显子，以寻找任何其他角质上皮蛋白突变。结果：蜂窝状混浊患者有Arg555Gln角上皮突变导致其RBCD，而地理性混浊患者没有；相反，他有一个新的角上皮突变（Arg124Leu），与他的家庭成员共分离。结论：以蜂窝状混浊为特征的RBCD变体是由Arg555Gln角上皮蛋白突变引起的，另一方面，发现了一种新的角上皮蛋白突变Arg124Leu导致以复发性上皮侵蚀和进行性上皮下混浊为特征的RBCD变体。密码子124是角膜上皮突变的热点，它是导致三种常染色体显性角膜营养不良的突变——晶格型I （Arg124Cys）、Avellino （Arg124 His）和具有地理而非蜂窝状不透明的RBCD变体（Arg124Leu）的位点。[J]中华眼科杂志1998；26:535-542。(C) 1998年Elsevier Science Inc。版权所有)。
PURPOSE: Two patients were diagnosed with Reis-Bucklers corneal dystrophy (RBCD), although the pattern and severity of corneal opacification differed. To see whether there was a genetic basis for these phenotypic variations, we analyzed beta ig-h3, the gene that codes for kerato-epithelin and that contains a mutation (Arg555Gln) that causes RBCD.METHODS: A 30-year-old man with honeycomb-shaped subepithelial opacities in his central cornea and a 25-year-old man with progressive subepithelial geographic opacities were both considered to have RBCD. We isolated genomic DNA from leukocytes of the two patients and their family members and screened for an Arg555Gln kerato-epithelin mutation. Then we analyzed all exons of the gene using the single-strand conformation polymorphism (SSCP) technique to search for any other kerato-epithelin mutations.RESULTS: The patient with honeycomb-shaped opacities had an Arg555Gln kerato-epithelin mutation that caused his RBCD, whereas the patient with geographic opacities did not; instead, he had a new kerato-epithelin mutation (Arg124Leu), which cosegregated with his family members.CONCLUSIONS: The variant of RBCD characterized by honeycomb-shaped opacities is caused by an Arg555Gln kerato-epithelin mutation, On the other hand, a new kerato-epithelin mutation, Arg124Leu, was found to cause the RBCD variant characterized by recurrent epithelial erosions and progressive geographic subepithelial opacification. Codon 124 is a hot: spot for kerato-epithelin mutations, where the mutations responsible for three autosomal dominant corneal dystrophies-lattice type I (Arg124Cys), Avellino (Arg124 His), and the variant of RBCD with geographic rather than honeycomb opacities (Arg124Leu)-are located. (Am J Ophthalmol 1998;126:535-542. (C) 1998 by Elsevier Science Inc. All rights reserved.).