Morley S M, White M I, Rogers M, Wasserman D, Ratajczak P, McLean W H I, Richard G
Department of Dermatology, Ninewells Hospital, Dundee, UK.
Br J Dermatol. 2005 Jun;152(6):1143-8. doi: 10.1111/j.1365-2133.2005.06610.x.
Erythrokeratodermia variabilis (EKV) is an autosomal dominant or recessive genodermatosis characterized by the coexistence of randomly occurring, transient, erythematous patches and hyperkeratosis of the skin. The disorder has been mapped to chromosome 1p35.1 but is genetically heterogeneous. EKV may be caused by pathogenic mutations in one of two neighbouring connexin genes, GJB3 and GJB4, encoding the gap junction proteins Cx31 and Cx30.3, respectively. Twelve distinct mutations identified to date cluster either at the cytoplasmic amino-terminus or in the four transmembrane domains.
To report a large family with EKV and an unrelated sporadic case.
DNA amplification and mutation analysis, followed by denaturing high-performance liquid chromatography to confirm the segregation of the mutations in the two families with EKV.
A novel, recurrent GJB3 mutation (625C-->T; L209F) was identified in the family with EKV and in the unrelated sporadic case.
This mutation is the first to affect a conserved residue in the cytoplasmic carboxy-terminus of any connexin gene with a cutaneous phenotype, emphasizing its structural and/or functional importance.
可变型红斑角化病（EKV）是一种常染色体显性或隐性遗传性皮肤病，其特征为随机出现的、短暂的红斑斑块与皮肤角化过度并存。该疾病已被定位到1p35.1染色体，但存在遗传异质性。EKV可能由两个相邻的连接蛋白基因GJB3和GJB4中的一个发生致病突变引起，这两个基因分别编码缝隙连接蛋白Cx31和Cx30.3。迄今为止鉴定出的12种不同突变集中在胞质氨基末端或四个跨膜结构域。
报告一个患有EKV的大家族和一例散发病例。
进行DNA扩增和突变分析，随后采用变性高效液相色谱法来确认EKV两个家族中突变的分离情况。
在患有EKV的家族和散发病例中均发现了一种新的、复发性的GJB3突变（625C→T；L209F）。
该突变是首个影响任何具有皮肤表型的连接蛋白基因胞质羧基末端保守残基的突变，凸显了其结构和/或功能的重要性。
