Wang P-G, Gao M, Lin G-S, Yang S, Lin D, Liang Y-H, Zhang G-L, Zhu Y-G, Cui Y, Zhang K-Y, Huang W, Zhang X-J
Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, China.
Clin Exp Dermatol. 2006 Jul;31(4):558-63. doi: 10.1111/j.1365-2230.2006.02134.x.
Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis characterized by multiple flat-topped, flesh-coloured papules on the dorsa of hands and feet, and punctuate keratoses on the palms and soles. A mutation in the ATP2A2 gene has been shown to be associated with AKV and with Darier's disease (DD).
To explore the molecular aetiology of AKV and DD.
We investigated the clinical and histological information in two families and a sporadic case with AKV and one family and a sporadic case with DD in China. Mutation analysis of ATP2A2 was performed by PCR and direct sequencing, and genotyping and linkage analysis performed using six polymorphic microsatellite markers spanning the locus at 12q23-12q24 containing ATP2A2.
Mutational analysis showed no mutation in ATP2A2 among the AKV patients, but we found two novel mutations (p.C318F and p.M719fs) in the DD patients. The genotyping and linkage analysis results revealed no linkage evidence of the locus at 12q23-12q24 in a large AKV family.
Our findings provide evidence for the genetic heterogeneity of AKV and demonstrate that mutations in genes other than ATP2A2 are responsible for AKV in a proportion of the Chinese population.
霍普夫疣状肢端角化病（AKV）是一种罕见的遗传性皮肤病，其特征为手足背部有多个平顶、肤色丘疹，手掌和足底有点状角化病。已证明ATP2A2基因突变与AKV及达里埃病（DD）相关。
探讨AKV和DD的分子病因。
我们调查了中国两个患有AKV的家系和1例散发病例以及1个患有DD的家系和1例散发病例的临床和组织学信息。通过PCR和直接测序对ATP2A2进行突变分析，并使用跨越12q23 - 12q24位点（包含ATP2A2）的6个多态性微卫星标记进行基因分型和连锁分析。
突变分析显示AKV患者中ATP2A2无突变，但我们在DD患者中发现了两个新突变（p.C318F和p.M719fs）。基因分型和连锁分析结果显示，在一个大型AKV家系中，12q23 - 12q24位点无连锁证据。
我们的研究结果为AKV的遗传异质性提供了证据，并表明在中国人群中，一部分AKV病例是由ATP2A2以外的基因突变引起的。
