角蛋白10突变致先天性大疱性鱼鳞病样红皮病1例

A case report of congenital bullous ichthyosiform erythroderma caused by a mutation of KRT10 gene

目的检测1例先天性大疱性鱼鳞病样红皮病(BCIE)患者KRT1和KRT10基因突变。方法提取患者及其家人外周血DNA,PCR扩增KRT1和KRT10基因编码区的全部外显子及其侧翼序列并测序,检测潜在的基因突变。结果该患者KRT10基因第1号外显子中的第467位碱基发生G→A杂合突变(c.467G>A),导致其编码的第156号氨基酸发生错义突变(p.Arg156His),患者父亲、母亲、姐姐均未发现该突变。患者及其母亲第7号外显子中的1654~1683位点发生重复突变,即NM_000421.5:c.1654_1683dup,该突变导致其编码的556至565位的氨基酸发生甘氨酸重复(p.Gly556_Gly565dup),该突变呈杂合状态,患者父亲、姐姐均未发现该突变,提示其为新发突变。KRT1基因未检测到突变。结论KRT10基因的c.467G>A错义突变是本例BCIE的致病原因,NM_000421.5:c.1654_1683dup重复突变可能不会导致BCIE。

Objective To identify KRT1 and KRT10 gene mutation in a patient with bullous ichthyosiform erythroderma(BCIE).Methods Peripheral bloods of the patient and her families were collected and DNAs were extracted.All coding exons and flanking sequence of the KRT1 and KRT10 genes were amplified by PCR.PCR products were directly sequenced to detect mutations.Potential gene mutations were detected by Sanger sequencing method.Results A heterozygous missense mutation c.467 G>A in exon 1 of KRT10 gene was identified,which led to the protein at position 156 unnormal(p.Arg156 His);The mutation was not found in the patient′s father,mother and sister.Another heterozygous repeat mutation NM_000421.5:c.1654_1683 dups in exon 7 of KRT10 gene in the patient and her mother between 1654 and 1684 was identified,and these mutations result in glycine repeats(p.Gly556_Gly565 dup)at positions 556 to 565,which was heterozygous.There was no mutation in other members of this family,so it was suggested that it was a new mutation.There was no mutation of KRT1 in all samples.Conclusion Mutation of c.467 G>A is the pathogenic cause of BCIE in this case and the mutation of 000421.5:c.1654_1683 dup of KRT10 gene may not be the pathogenic cause.