O'Driscoll J, Muston G C, McGrath J A, Lam H M, Ashworth J, Christiano A M
Stepping Hill Hospital, Stockport NHS Trust, UK.
Clin Exp Dermatol. 2002 May;27(3):243-6. doi: 10.1046/j.1365-2230.2002.01031.x.
Vohwinkel syndrome (VS) is a family of genodermatoses which exhibits extensive clinical and genetic heterogeneity. Here, we studied a pedigree originating from the UK with typical features of the ichthyotic variant of VS and identified a recurrent insertion mutation in the loricrin gene resulting in a mutant polypeptide with an unusual C terminus. Functional studies in transgenic mice have shown that the accumulation of mutant loricrin in the nucleus appears to interfere with the later stages of epidermal differentiation, thereby explaining the clinical manifestations of ichthyosis, keratoderma and pseudoainhum. Our findings extend the body of evidence implicating mutations in the loricrin gene as the underlying cause of VS.
Vohwinkel综合征（VS）是一类遗传性皮肤病，具有广泛的临床和遗传异质性。在此，我们研究了一个来自英国的家系，其具有VS鱼鳞病变异型的典型特征，并在loricrin基因中鉴定出一个反复出现的插入突变，该突变导致了一种具有异常C末端的突变多肽。对转基因小鼠的功能研究表明，突变型loricrin在细胞核中的积累似乎会干扰表皮分化的后期阶段，从而解释了鱼鳞病、角化皮病和假并指（趾）畸形的临床表现。我们的研究结果进一步证明了loricrin基因突变是VS的潜在病因。
