Institute of Human Genetics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Center for Cornification Disorders, Freiburg Center for Rare Diseases, Medical Center, University of Freiburg, 79106 Freiburg, Germany.
Genes (Basel). 2023 Mar 15;14(3):717. doi: 10.3390/genes14030717.
Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in , , , , , , , , , and . The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in . Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in . Our study comprises 34 novel mutations in , expanding the mutational spectrum of -associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI.
常染色体隐性先天性鱼鳞病（ARCI）是一种非综合征性先天性角化障碍，其特征为皮肤异常鳞化。三种主要表型为层状鱼鳞病、先天性鱼鳞病红皮病和丑角鱼鳞病。ARCI 是由 、 、 、 、 、 、 、 和 这 9 个基因的双等位基因突变引起的。ARCI 中最严重的形式——丑角鱼鳞病是由 基因突变引起的。该基因的突变也可导致先天性鱼鳞病红皮病或层状鱼鳞病。我们报告了一个由 基因双等位基因突变引起的 ARCI 患者的大队列，共 64 例。我们的研究包括 34 个新的 基因突变，使 -相关 ARCI 的突变谱扩展至 217 个突变。在这些突变中，我们发现了可能的突变热点 c.4541G>A，p.(Arg1514His)和 c.4139A>G，p.(Asn1380Ser)。证明了表型与基因突变对蛋白质功能的影响之间存在相关性。两个等位基因上的功能丧失突变通常导致丑角鱼鳞病，而双等位基因上的错义突变主要导致 CIE 或 LI。
