Keratin 1 gene mutation detected in epidermal nevus with epidermolytic hyperkeratosis
Keratin 1 gene mutation detected in epidermal nevus with epidermolytic hyperkeratosis
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DOI：
10.1038/sj.jid.5700712
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发表时间：
2007-06-01
影响因子：
6.5
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
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作者：
Tsubota, Akiko;Akiyama, Masashi;Shimizu, Hiroshi
自1994年以来，已报道了4例角蛋白10基因突变引起的表皮痣伴表皮角化过度症（EH），但尚未报道角蛋白1（K1）基因突变。我们检测到一个10岁的日本男性表皮痣与EH的K1基因（KRT1）突变。患者显示边界清楚的疣状角化过度斑块，主要位于躯干，覆盖整个体表的15%。手掌或脚掌未见角化过度。他没有皮肤病家族史。他的病变皮肤表现出典型的颗粒变性，超微结构，聚集角蛋白丝观察到在上表皮。从皮损皮肤提取的基因组DNA的直接序列分析揭示了KRT 1中的杂合5 '供体剪接位点突变c.591 + 2T > A。在患者外周血白细胞或其他家庭成员的基因组DNA样本中未检测到这种突变。相同的剪接突变先前报道在一个家庭掌跖角化病和轻度鱼鳞病，并证明导致22个氨基酸缺失p.Val175_Lys196del在H1和1A域的K1。据我们所知，目前的病人是第一个报告的情况下，表皮痣与高血压引起的K1基因突变的马赛克模式。
Since 1994, four cases of epidermal nevus with epidermolytic hyperkeratosis (EH) caused by keratin 10 gene mutations have been reported, although no keratin 1 (K1) gene mutation has yet been reported. We detected a K1 gene (KRT1) mutation in epidermal nevus with EH in a 10-year-old Japanese male. The patient showed well-demarcated verrucous, hyperkeratotic plaques mainly on the trunk, covering 15% of the entire body surface. No hyperkeratosis was seen on the palms or soles. He had no family history of skin disorders. His lesional skin showed typical granular degeneration and, ultrastructurally, clumped keratin filaments were observed in the upper epidermis. Direct sequence analysis of genomic DNA extracted from lesional skin revealed a heterozygous 5 ' donor splice site mutation c.591 + 2T > A in KRT1. This mutation was not detected in genomic DNA samples from the patient's peripheral blood leukocytes or those of other family members. The identical splice mutation was previously reported in a family with palmoplantar keratoderma and mild ichthyosis, and was demonstrated to result in a 22 amino-acid deletion p.Val175_Lys196del in the H1 and 1A domains of K1. To our knowledge, the present patient is the first reported case of epidermal nevus associated with EH caused by a K1 gene mutation in a mosaic pattern.