A novel heterozygous missense mutation in the SASH1 gene is associated with dyschromatosis universalis hereditaria in a pedigree

Objective To investigate clinical features and molecular genetic basis of dyschromatosis universalis hereditaria (DUH) in a pedigree. Methods A detailed genetic survey and a physical examination were performed for available members in a pedigree with DUH. In addition, reflectance confocal microscopy and histopathology were carried out to observe skin lesions of the proband. Blood samples were collected from 8 family members (including 5 patients with DUH and 3 unaffected members) and 200 unrelated healthy human controls. The FlexiGene DNA kit was used to extract genomic DNA from these blood samples, and PCR was performed to amplify all coding exons and their flanking sequences of SASH1 and ABCB6 genes followed by direct DNA sequencing. Results DUH was inherited in an autosomal dominant manner in this pedigree, and occurred within 1 year after birth in 9 patients. Lesions initially appeared on the face, then gradually spread to the whole body. Among 8 surviving patients, 7 presented with irregularly shaped light brown to puce macules complicated by uniform hypopigmentation of the remaining skin, and only the elder sister of the proband showed generalized hyperpigmented macules mingled with hypopigmented macules in a reticular pattern. No abnormality was observed in oral mucosa, nails or teeth, and general status was good in the 8 patients. DNA sequencing revealed a novel heterozygous missense mutation (c.1761C > G, p.Ser587Arg) in exon 15 of the SASH1 gene in the 5 available patients, but not in the 3 unaffected individuals or 200 healthy controls. No mutation was found in the ABCB6 gene in any of the 8 family members. Conclusions Heterogeneity exists in clinical features and molecular genetic basis of DUH. The heterozygous missense mutation p.S587R in the SASH1 gene might be responsible for DUH in this family. Key words: Autosomal-dominant; Heterozygote; Mutation; Genetics; Han nationality; Genes, SASH1; Dyschromatosis universalis hereditaria