PDF(Pubmed)
Abstract：
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 ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. 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 ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-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.
摘要：
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质化疾病，其特征是皮肤异常结垢。三种主要表型是层状鱼鳞病，先天性鱼鳞状红皮病，和丑角鱼鳞病.ARCI是由ABCA12，ALOX12B，ALOXE3、CERS3、CYP4F22、NIPAL4、PNPLA1、SDR9C7、SULT2B1和TGM1。最严重的ARCI，丑角鱼鳞病，是由ABCA12的突变引起的。该基因的突变也可导致先天性鱼鳞状红皮病或层状鱼鳞病。我们提出了一个大型队列，包括64例ARCI携带ABCA12双等位基因突变的患者。我们的研究包括ABCA12中的34个新突变，将ABCA12相关ARCI的突变谱扩展到217个突变。在这些中，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的相关性。两个等位基因上的功能丧失突变通常会导致丑角鱼鳞病，而双等位基因错义突变主要导致CIE或LI。
