Open AccessFrameshift variant in MITF gene in a large family with Waardenburg syndrome type II and a co-segregation of a C2orf74 variant
Author(s) -
Maan Abdullah Albarry,
Muhammad Latif,
Ahdab Qasem Alreheli,
Mohammed Awadh,
Ahmad Almatrafi,
Alia M. Albalawi,
Sulman Basit
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0246607
Subject(s) - genetics , waardenburg syndrome , microphthalmia associated transcription factor , sanger sequencing , exome sequencing , biology , frameshift mutation , missense mutation , single nucleotide polymorphism , gene , genotyping , exome , snp , snp genotyping , candidate gene , mutation , phenotype , genotype , transcription factor
Waardenburg syndrome (WS) is a hereditary disorder affecting the auditory system and pigmentation of hair, eyes, and skin. Different variants of the disease exist with the involvement of mutation in six genes. The aim of the study is to identify the genetic defects underlying Waardenburg syndrome in a large family with multiple affected individuals. Here, in this study, we recruited a large family with eleven affected individuals segregating WS type 2. We performed whole genome SNP genotyping, whole exome sequencing and segregation analysis using Sanger approach. Whole genome SNP genotyping, whole exome sequencing followed by Sanger validation of variants of interest identified a novel single nucleotide deletion mutation (c.965delA) in the MITF gene. Moreover, a rare heterozygous, missense damaging variant (c.101T>G; p.Val34Gly) in the C2orf74 has also been identified. The C2orf74 is an uncharacterized gene present in the linked region detected by DominantMapper. Variants in MITF and C2orf74 follows autosomal dominant segregation with the phenotype, however, the variant in C2orf74 is incompletely penetrant. We proposed a digenic inheritance of variants as an underlying cause of WS2 in this family.