Clinical manifestations and novel pathogenic variants in SOX10 in eight Danish probands with Waardenburg syndrome

Marika F Moldenæs, Nanna D Rendtorff, Lone S Hindbæk, Pernille M Tørring, Øivind Nilssen, Lisbeth Tranebjærg

Abstrakt

The SRY-related HMG box gene 10 (SOX10), located on 22q13.1, encodes a member of the SOX family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate and differentiation. SOX10 is one of the six causal genes for Waardenburg syndrome, which is a dominantly inherited auditory-pigmentary disorder characterized by sensorineural hearing impairment and abnormal pigmentation of the hair, skin and iris. Waardenburg syndrome is categorized into four subtypes based on clinical features (WS1-WS4). Here we present eight families (eleven patients) harboring pathogenic variants in SOX10. The patients displayed both allelic and clinical variability: bilateral profound hearing impairment (11/11), malformations of the semicircular canals (5/11), motor skill developmental delay (5/11), pigmentary defects (3/11) and Hirschsprung's disease (3/11) were some of the clinical manifestations observed. The patients demonstrate a spectrum of pathogenic SOX10 variants, of which six were novel (c.267del, c.299_300insA, c.335T >C, c.366_376del, c.1160_1179dup, and exon 3-4 deletion), and two were previously reported (c.336G>A and c.422T>C). Six of the variants occurred de novo whereas two were dominantly inherited. The pathogenic SOX10 variants presented here add novel information to the allelic variability of Waardenburg syndrome and illustrate the considerable clinical heterogeneity.

OriginalsprogEngelsk
Artikelnummer104265
TidsskriftEuropean Journal of Medical Genetics
Vol/bind64
Udgave nummer9
Sider (fra-til)104265
ISSN1769-7212
DOI
StatusUdgivet - sep. 2021

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