Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene.

Li Li,Yu Zhang,Jing Ma,Yuan-Tao Zhou,Biao Ruan,Xiao-Li He,Tie-Song Zhang,Lin Zhang,Quan-Dong Chen

doi:10.1042/bsr20193375

Abstract

Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to play an important role in the pathogenesis of WS. We investigated one family of five members, with four patients exhibiting the classic form of WS2, whose DNA samples were analyzed by the technique of Whole-exome sequencing (WES). From analysis of WES data, we found that both the mother and all three children in the family have a heterozygous mutation on the Sex Determining Region Y - Box 10 (SOX10) gene. The mutation was c.298_300delinsGG in exon 2 of SOX10 (NM_006941), which leads to a frameshift of nine nucleotides, hence the amino acids (p. S100Rfs*9) are altered and the protein translation may be terminated prematurely. Further flow cytometry confirmed significant down-regulation of SOX10 protein, which indicated the SOX10 gene mutation was responsible for the pathogenesis of WS2 patients. In addition, we speculated that some other mutated genes might be related to disease phenotype in this family, which might also participate in promoting the progression of WS2.

Highlights

Waardenburg syndrome (WS) was first reported in detail in 1951, a congenital hereditary disease characterized by sensorineural deafness and iris abnormalities [1]
We described a Chinese pedigree with clinical features of WS2
As shown in our results, the mother (I-2) and her two children’s (II-2 and II-3) left eye appeared sapphire blue, while the third child’s iris color was brown, which is considered normal in Chinese population

Summary

Introduction

Waardenburg syndrome (WS) was first reported in detail in 1951, a congenital hereditary disease characterized by sensorineural deafness and iris abnormalities [1]. It is known as the auditory-pigmentary deficient syndrome. WS accounts for 2–5% of congenital deafness, and its incidence is 0.9–2.8% in deaf people [2]. In addition to the two most common phenotypes of sensorineural deafness and iris abnormality, WS1 is distinguished from WS2 with the W index > 1.95. The presence of limb abnormalities distinguishes WS3, and the association with Hirschsprung disease (aganglionic megacolon) is the feature of WS4 [3,4]. WS2 mainly manifests in congenital sensorineural deafness and pigment abnormalities without additional features, and symptoms of WS2 are milder than the other three

Methods

Results

Conclusion