Abstract: 【Abstract】 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 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.

Key words: Skin pigmentation, Skin diseases, genetic, Dowling-Degos disease, KRT5 gene