Dowling-Degos病1家系KRT5基因新突变分析

Mutation analysis of the KRT5 gene in a Chinese pedigree with Dowling-Degos disease

目的分析Dowling-Degos病1家系KRT5基因突变情况。方法收集先证者临床资料,调查先证者家族3代共12人信息,采集先证者和8例家系成员以及家系以外50例无亲缘关系的健康人外周血,提取基因组DNA行全外显子测序后与人类基因组KRT5、POFUT1及POGLUT1序列进行比对。结果本家系有3例患者,分别为先证者及其父亲和祖母(去世)。先证者及其父亲临床表现为皱褶部网状色素沉着,以胸腹皱褶部位为重,且KRT5基因第一外显子均存在c.165T>A杂合无义突变,其他家系成员及健康对照均未发现此突变,所有受试者POFUT1及POGLUT1基因检测未见异常。结论本研究新发现1处KRT5基因c.165T>A突变,导致先证者及其父Dowling-Degos病。

Objective To investigate mutations in the KRT5 gene in a pedigree with Dowling-Degos disease.Methods Clinical data were collected from the proband,and a survey was conducted in 12 members in 3 generations of the family.Peripheral blood samples were obtained from the proband,8 family members and 50 unrelated healthy individuals,genomic DNA was extracted for whole-exome sequencing,and sequencing results were compared with the published sequences of human KRT5,POFUT1 and POGLUT1 genes.Results There were 3 patients in this family,including the proband,his father and deceased grandmother.The proband and his father clinically presented with reticular pigmentation in the skinfolds,especially the chest and abdomen skinfolds.A novel heterozygous nonsense mutation c.165T>A was identified in exon 1 of the KRT5 gene in the proband and his father,but not in other family members or healthy controls.No abnormality was found in the POFUT1 or POGLUT1 gene in any subjects.Conclusion A novel heterozygous nonsense mutation c.165T>A was identified in the KRT5 gene,and may contribute to the clinical phenotype of the proband and his father with Dowling-Degos disease.