Abstract
BackgroundDyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH.MethodsSanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations.ResultsA novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6.ConclusionAlthough the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.
Highlights
Dyschromatosis universalis hereditaria (DUH) is an infrequent hereditary dermatosis accompanied by generalized mottled macules with hypopigmention and hyperpigmention
According to the Sanger sequencing results, we identified a previously unreported heterozygous missense mutation [(hg19) chr6:g.148852762G>A/c.1529G>A/p.S510N] in exon 13 of the SASH1 gene (NM_015278) in family members II3, III6, and III9 (Fig. 3), and this mutation was not present in the other four unaffected individuals (II4, II9, III5, and III11; the Sanger sequencing traces are shown in Additional file 2)
This variant was the only one that cosegregated perfectly with the phenotype in this family, and the variant was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man (OMIM), ClinVar, or The 1000 Genomes Project (1000G) databases
Summary
Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Dyschromatosis universalis hereditaria (DUH) is an infrequent hereditary dermatosis accompanied by generalized mottled macules with hypopigmention and hyperpigmention. Cao et al BMC Med Genomics (2021) 14:168 confirmed that the gene associated with dominant dyschromatosis symmetrica hereditaria (DSH) maps to chromosome 6q24.2-q25.2 [1]. In 2013, Zhang et al identified a third DUH-related pathogenic region, 2q33.3-q36.13, and confirmed that ACBC6, located at 2q35, is the pathogenic gene of DUH [4]
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