Identification of a Novel Mutation in SASH1 Gene in a Chinese Family With Dyschromatosis Universalis Hereditaria and Genotype-Phenotype Correlation Analysis.

Nan Wu,Peiguang Wang,Xiaodong Zheng,Xiuxiu Li,Lili Tang,Min Gao,Yuwei Dai

doi:10.3389/fgene.2020.00841

Abstract

Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by mottled hyperpigmented and hypopigmented macules. SASH1 and ABCB6 have been identified as the causative genes for this disorder. We performed whole exome sequencing on a Chinese family with DUH and genotype-phenotype correlation analysis in DUH and lentiginous phenotype patients. A novel heterozygous missense mutation p.Q518P in SASH1 gene was detected in this family. A majority of patients with SASH1 mutations presented as a distinct clinical phenotype clearly different from that in patients with ABCB6 mutations. Our findings further enrich the reservoir of SASH1 mutations in DUH. The clinical phenotypic difference between SASH1 and ABCB6 variants is suggestive of a close phenotype-genotype link in DUH.

Highlights

Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis which is characterized by generalized hyperpigmented macules mixed with hypopigmented macules in a reticular pattern, which usually appears from infancy or early childhood
The substitution p.Q518P was predicted to be “deleterious” with a score of 0.001 in SIFT2 and “probably damaging” with a score of 0.999 in PolyPhen2.3 None of possible pathogenic variations was present in ABCB6 gene
Comparing the phenotype of SASH1 variants with that of ABCB6 variants in DUH, we found a distinct difference in clinical phenotype between them

Summary

INTRODUCTION

Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis which is characterized by generalized hyperpigmented macules mixed with hypopigmented macules in a reticular pattern, which usually appears from infancy or early childhood. It was firstly described in 1933 by Ichikawa and Hiraga. DUH shares a typical phenotypic feature with dyschromatosis symmetrica hereditaria (DSH), that is reticulate hyperpigmentation and hypopigmentation on extremities. DUH was rarely accompanied with other abnormalities, such as neurosensory hearing loss, adermatoglyphia, photosensitivity, primary ovarian failure, insulin-dependent diabetes, renal failure, and ocular abnormalities, Dowling-Degos disease (DDD) (Yang and Wong, 1991; Sandhu et al, 2004; Bhoyar et al, 2015; Rojhirunsakool and Vachiramon, 2015; Gupta, 2016; Jayanthi et al, 2016)

A Novel SASH1 Mutation in DUH

METHODS

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT