GJB2 mutations in keratitis-ichthyosis-deafness syndrome including its fatal form
GJB2 mutations in keratitis-ichthyosis-deafness syndrome including its fatal form
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DOI：
10.1002/ajmg.a.30515
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发表时间：
2005-03-01
影响因子：
2
通讯作者：
Rittinger, O
中科院分区：
文献类型：
--
作者：
Janecke, AR;Hennies, HC;Rittinger, O
角膜炎-鱼鳞病-耳聋综合征（KID；MIM 148210）是一种罕见的先天性疾病，其特征为血管化角膜炎、感音神经性听力损失 (HL) 和进行性红斑角化病。据报道，临床变异性包括第一年出现致命的 KID 病程。最近发现，编码连接蛋白 26 的 GJB2 种系错义突变可导致 14 名无关的青少年和成人患者出现 KID。我们在一名表现出致命疾病的患者中发现了新的 GJB2 突变 G45E。其他五个连接蛋白和线粒体基因未检测到突变。 G45E 突变此前并未在白种人患者中报道，但在日本常染色体隐性非综合征型 HL 患者中却是第三常见的 GJB2 突变（占疾病等位基因的 16%）。这一发现表明，同一 GJB2 突变根据遗传背景有不同的作用模式。我们对来自奥地利的无关 KID 患者的不同临床病程的观察进一步证实了这一假设，这些患者在 GJB2 中携带常见的 D50N 突变。 (C) 2005 Wiley-Liss, Inc.
Keratitis-ichthyosis-deafness syndrome (KID; MIM 148210) is a rare congenital disorder characterized by vascularizing keratitis, sensorineural hearing loss (HL), and progressive erythrokeratoderma. Clinical variability including a fatal course of KID in the first year of life has been reported. Germline missense mutations in GJB2, encoding connexin-26, were recently found to cause KID in 14 unrelated juvenile and adult patients. We identified a de novo GJB2 mutation G45E in a patient displaying the fatal form of the disease. No mutations were detected in five other connexin and mitochondrial genes. The G45E mutation was not reported previously in Caucasian patients but was the third most common GJB2 mutation (16% of disease alleles) in Japanese patients with autosomal recessive non-syndromic HL. This finding suggests different modes of action of the same GJB2 mutation depending on the genetic background. This hypothesis was further substantiated by our observation of a variable clinical course in unrelated KID patients from Austria harboring the common D50N mutation in GJB2. (C) 2005 Wiley-Liss, Inc.