A keratin 14 mutational hot spot for epidermolysis bullosa simplex, Dowling-Meara: implications for diagnosis.
A keratin 14 mutational hot spot for epidermolysis bullosa simplex, Dowling-Meara: implications for diagnosis.
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DOI：
10.1111/1523-1747.ep12365079
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发表时间：
1993-08
期刊：
影响因子：
--
通讯作者：
V. Sybert;K. Stephens
中科院分区：
文献类型：
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作者：
V. Sybert;K. Stephens
摘要 最近，报道了两名 Doling-Meara 亚型单纯性大疱性表皮松解症 (EBS-DM) 患者的角蛋白 14 基因密码子 125 存在不同突变。为了确定这些是否是常见突变，我们使用单核苷酸引物延伸筛选了 10 名 EBS-DM 患者及其家人。十名不相关的 EBS-DM 患者中有四名在密码子 125 的第 434 位碱基对处有 G→-A 取代，而十分之一的病例在同一密码子的第 433 位有 C→-T 取代。 G434A 改变与两个多代家庭中的疾病共分离；没有检测到重组事件。在这两个家族中，连锁分析提供了支持 G434A 和 EBS-DM 表型之间连锁的重要证据，LOD 评分为 3.29，重组率为 0%。在三名不相关的散发性 EBS-DM 患者中发现的密码子 125 替换在其临床上未受影响的父母中没有发现。总之，这些数据提供了令人信服的遗传证据，证明密码子 125 替换是 EBS-DM 的因果关系。 EBS-DM 患者中该位点的高频率突变现在使得基于 DNA 的这种疾病诊断成为可能。
Abstract Recently, two patients with the Dowling-Meara subtype of epidermolysis bullosa simplex (EBS-DM) were reported with different mutations in codon 125 of the keratin 14 gene. To determine whether these are common mutations, we screened ten EBS-DM patients and their families using single nucleotide primer extension. Four of ten unrelated EBS-DM patients had a G→-A substitution at base pair 434 of codon 125, whereas one case out of ten had a C→-T substitution at position 433 of the same codon. The G434A alteration cosegregated with the disorder in two multigenerational families; no recombination events were detected. In these two families, linkage analysis provided significant evidence in favor of linkage between G434A and the EBS-DM phenotype, with a LOD score of 3.29 at a recombination rate of 0%. Codon 125 substitutions identified in three unrelated sporadic EBS-DM patients were not found in their clinically unaffected parents. Together, these data provide compelling genetic evidence that the codon 125 substitutions are causal for EBS-DM. The high frequency of mutation at this site in individuals with EBS-DM now makes DNA-based diagnosis of this disorder feasible.