Diffuse and focal palmoplantar keratoderma can be caused by a keratin 6c mutation
Diffuse and focal palmoplantar keratoderma can be caused by a keratin 6c mutation
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DOI：
10.1111/j.1365-2133.2011.10552.x
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发表时间：
2011-12-01
影响因子：
10.3
通讯作者：
Sawamura, D.
中科院分区：
文献类型：
--
作者：
Akasaka, E.;Nakano, H.;Sawamura, D.
掌跖角化病（PPKs）是一大类遗传性皮肤病，包括近60种遗传上不同的疾病。它们的特征是手掌和脚掌角化过度，伴或不伴掌跖外角化过度病变。局灶性PPK是先天性甲肥厚的标志之一，这是一种罕见的常染色体显性遗传病，由角蛋白基因KRT6A、KRT6B、KRT16或KRT17突变引起。最近，在三个有轻微或无指甲变化的局灶性PPK家族中发现了KRT6C的框内缺失突变。我们在此报告了一个在日本PPK家族中发现的新的KRT6C突变，该家族具有表型异质性，不仅表现为局灶性角化过度，而且表现为弥漫性角化过度。先证者的脚底有弥漫性角化过度，手掌有小的局灶性角化过度，而另外两个受影响的个体的脚底有局灶性角化过度。所有三名患者都是KRT 6C中c.1414G>A的杂合子，预测会导致p.Glu472Lys。这些发现强烈表明，筛查非表皮炎性弥漫性PPK患者，其中致病性突变尚未确定，可能会发现KRT6C突变。
The palmoplantar keratodermas (PPKs) are a large group of genodermatoses comprising nearly 60 genetically distinct diseases. They are characterized by hyperkeratosis on the palms and soles with or without extrapalmoplantar hyperkeratotic lesions. Focal PPK is one of the hallmarks of pachyonychia congenita, a rare autosomal dominant disorder resulting from mutations in the keratin genes KRT6A, KRT6B, KRT16 or KRT17. Recently, in-frame deletion mutations of KRT6C have been identified in three families with focal PPK with slight or no nail changes. We report here a novel KRT6C mutation identified in a Japanese family with PPK with phenotypic heterogeneity, presenting with not only focal but also diffuse hyperkeratosis. The proband had diffuse hyperkeratosis on the soles and small focal hyperkeratoses on the palms, while the two other affected individuals showed focal hyperkeratoses on the soles. All three patients were heterozygotes for c.1414G>A in KRT6C, predicted to result in p.Glu472Lys. These findings strongly suggest that screening of patients with nonepidermolytic diffuse PPK, in whom the pathogenic mutations are yet to be determined, might identify mutations in KRT6C.