Kerato-epithelin mutations in four 5q31-linked corneal dystrophies
Kerato-epithelin mutations in four 5q31-linked corneal dystrophies
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DOI：
10.1038/ng0397-247
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发表时间：
1997-03-01
期刊：
影响因子：
30.8
通讯作者：
Schorderet, DF
中科院分区：
文献类型：
--
作者：
Munier, FL;Korvatska, E;Schorderet, DF
颗粒状营养不良Groenouw I型（CDGG 1）、Reis-Bucklers I型（CDL 1）、格子型I型（CDL 1）和Avellino（ACD）是四种5 q31连锁的人类常染色体显性角膜营养不良。临床上，他们表现出渐进性角膜混浊，导致严重的视力障碍。沉积物的性质仍然未知，尽管淀粉样蛋白病因归因于最后两个。我们产生了连接区域的YAC重叠群，并在cDNA选择后，回收了β ig-h3基因。在六个受影响的家庭中，我们发现了错义突变。所有检测到的突变均发生在两个精氨酸密码子的CpG二核苷酸处：一个CDGG 1中的R555 W，一个CDRB中的R555 Q，两个CDL 1中的R124 C和两个ACD家族中的R124 H。这表明，由于后两种疾病的特征在于淀粉样蛋白沉积，R124突变的角膜上皮素（β ig-h3的产物）形成淀粉样蛋白生成中间体，沉淀在角膜中。我们的数据为5 q31连锁的角膜营养不良建立了一个共同的分子起源。
Granular dystrophy Groenouw type I (CDGG1), Reis-Bucklers (CDL1), lattice type I (CDL1) and Avellino (ACD) are four 5q31-linked human autosomal dominant corneal dystrophies. Clinically, they show progressive opacification of the cornea leading to severe visual handicap. The nature of the deposits remains unknown in spite of amyloid aetiology ascribed to the last two. We generated a YAC contig of the linked region and, following cDNA selection, recovered the beta ig-h3 gene. In six affected families we identified missense mutations. All detected mutations occurred at the CpG dinucleotide of two arginine codons: R555W in one CDGG1, R555Q in one CDRB, R124C in two CDL1 and R124H in two ACD families. This suggests, as the last two diseases are characterized by amyloid deposits, that R124 mutated kerato-epithelin (the product of beta ig-h3) forms amyloidogenic intermediates that precipitate in the cornea. Our data establish a common molecular origin for the 5q31-linked corneal dystrophies.