四种遗传性鱼鳞病基因型与临床表型的相关性分析

目的对四种鱼鳞病(寻常型鱼鳞病;X性-联鱼鳞病;板层状鱼鳞病;大疱性鱼鳞病)的致病基因进行精细定位,并分析其基因型与临床表型的关系。方法对四种鱼鳞病各1例患者进行临床表型分析以及外周血DNA直接测序检测鱼鳞病FLG基因、STS基因、TGM1基因和K1,K10角蛋白基因的突变位点。结果①寻常型鱼鳞病患者在FLG基因的外显子5的第278位有G-T突变,613位有G-A突变。②板层状鱼鳞病患者TGM1基因外显子3的第504位碱基有C-T突变,使第142位氨基酸由精氨酸(R)转变为半胱氨酸(C),即R142C错义突变;外显子7的第1122位碱基有C-T突变,使348位氨基酸由精氨酸(R)突变为终止密码(R348X),导致其编码的蛋白缺失了C端的470个氨基酸。③X-性联鱼鳞病患者STS基因完全缺失。④大疱性鱼鳞病患者外显子5的第242碱基存在A-C突变,外显子6的第599位碱基均存在A-G突变,导致K1蛋白第633位氨基酸由赖氨酸(Lys)变为精氨酸(Arg)。结论鱼鳞病患者临床表型的不同与致病基因的突变位点密切相关。

Analysis on the Genotype and Clinical Phenotype Correlations of Four Style Heritage Ichthyosis

Objective To identify the mutation genes of paitents and their families with ichthyosis vulgaris;X-linked ichthyosis;lamellar ichthyosis;epidermolytic hyperkeratosis ichthyosis and to analyse the possible correlations between genotype and phenotype.Methods The genomic DNA was extracted from the proband and his family members.PCR amplification of all the encoding exons and adjacent splice sites of FLG gene,STS gene,TGM1 gene and Keratin gene.Mutationscanning was carried out via direct bidirectional DNA sequencing.Results ① There was a G278T mutation located in exon 5 and a G613A mutation located in exon 6 of patients with IV.② The patient with XLI had a complete deletion of STS gene.③ There was a C504T mutation located at codon 142(R142C) in exon 3 of TGM1 gene of lamellar ichthyosis patient,and a nonsense mutation of C1122T located in exon 7,which caused a premature terminationof R348X and a defective polypeptide truncated by 470 amino acids in C-terminus.④ Sequencing proved that there was a A504C mutation located in exon 5 and a A599G mutation located in exon 6.single heterozygous point mutation in K1 genes leading to an amino acid alteration of Lys to Arg in patients with Bullous congenital ichthyosiform erythroderma.Conclusions The different clinical features and phenotype expression have close relationship with the different mutation genes in lchthyosis patients.