Mutation in type II procollagen (COL2A1) that substitutes aspartate for glycine alpha 1-67 and that causes cataracts and retinal detachment: evidence for molecular heterogeneity in the Wagner syndrome and the Stickler syndrome (arthro-ophthalmopathy)
Mutation in type II procollagen (COL2A1) that substitutes aspartate for glycine alpha 1-67 and that causes cataracts and retinal detachment: evidence for molecular heterogeneity in the Wagner syndrome and the Stickler syndrome (arthro-ophthalmopathy)
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发表时间：
1993-07
影响因子：
9.8
通讯作者：
J. Korkko;P. Ritvaniemi;Leena Haataja;Helena;Kddridinen;Kivirikko;Darwin J. Prockop;L. Ala-Kokko
中科院分区：
文献类型：
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作者：
J. Korkko;P. Ritvaniemi;Leena Haataja;Helena;Kddridinen;Kivirikko;Darwin J. Prockop;L. Ala-Kokko
在一个早发性白内障、视网膜格子状变性和视网膜脱离的家族成员中进行了II型前胶原（COL 2A 1）基因突变的研究。他们没有提示非眼部组织受累的症状，而这在Stickler综合征中是典型的。PCR扩增COL 2A 1基因，变性梯度凝胶电泳分析产物。结果提示外显子10的一个等位基因突变。该片段的测序显示了一个单碱基突变，该突变将位置α 1-67处的甘氨酸密码子转化为天冬氨酸。在可用于研究的三个受影响的家庭成员中发现了这种突变，但在未受影响的成员或100个无关个体中没有发现。与先前报道的突变的比较表明，在COL 2A 1基因中引入提前终止密码子的突变是Stickler综合征的常见原因，但是COL 2A 1基因中用大体积氨基酸的密码子替换甘氨酸密码子的突变可以产生从致死性软骨发育不良到仅涉及眼组织的综合征的广泛的病症，类似于瓦格纳在1938年首次描述的家族综合征。
A search for mutations in the gene for type II procollagen (COL2A1) was carried out in affected members of a family with early-onset cataracts, lattice degeneration of the retina, and retinal detachment. They had no symptoms suggestive of involvement of nonocular tissues, as is typically found in the Stickler syndrome. The COL2A1 gene was amplified with PCR, and the products were analyzed by denaturing gradient gel electrophoresis. The results suggested a mutation in one allele for exon 10. Sequencing of the fragment demonstrated a single-base mutation that converted the codon for glycine at position alpha 1-67 to aspartate. The mutation was found in three affected members of the family available for study but not in unaffected members or 100 unrelated individuals. Comparison with previously reported mutations suggested that mutations introducing premature termination codons in the COL2A1 gene are a frequent cause of the Stickler syndrome, but mutations in the COL2A1 gene that replace glycine codons with codons for bulkier amino acid can produce a broad spectrum of disorders that range from lethal chondrodysplasias to a syndrome involving only ocular tissues, similar to the syndrome in the family originally described by Wagner in 1938.