Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Br J Dermatol. 2011 Dec;165(6):1290-2. doi: 10.1111/j.1365-2133.2011.10552.x.
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.
掌跖角化过度症（PPK）是一组大型遗传性皮肤病，包括近 60 种具有遗传异质性的疾病。其特征是手掌和脚底出现过度角化，伴或不伴有掌跖外过度角化病变。局灶性 PPK 是先天性厚甲症的特征之一，这是一种罕见的常染色体显性遗传疾病，由角蛋白基因 KRT6A、KRT6B、KRT16 或 KRT17 的突变引起。最近，在三个局灶性 PPK 伴轻度或无指甲改变的家族中发现了 KRT6C 的框内缺失突变。我们在此报告了一个具有表型异质性的日本 PPK 家族中发现的新型 KRT6C 突变，其特征不仅是局灶性，而且是弥漫性过度角化。先证者的脚底有弥漫性过度角化，手掌上有小的局灶性过度角化，而另外两名受影响的个体的脚底有局灶性过度角化。这三名患者均为 KRT6C c.1414G>A 的杂合子，预计会导致 p.Glu472Lys。这些发现强烈提示，对尚无明确致病突变的非大疱性弥漫性 PPK 患者进行筛查，可能会发现 KRT6C 的突变。
