Author:
Li Sijun,Qin Mengyao,Mao Shuang,Mei Lingyun,Cai Xinzhang,Feng Yong,He Chufeng,Song Jian
Abstract
Abstract
Background
Waardenburg syndrome (WS) is the most common form of syndromic deafness with phenotypic and genetic heterogeneity in the Chinese population. This study aimed to clarify the clinical characteristics and the genetic cause in eight Chinese WS families (including three familial and five sporadic cases). Further genotype–phenotype relationships were also investigated.
Methods
All probands underwent screening for the known WS-related genes including PAX3, SOX10, MITF, EDNRB, EDN3, and SNAI2 using next-generation sequencing to identify disease-causing genes. Further validation using Sanger sequencing was performed. Relevant findings for the associated genotype–phenotype from previous literature were retrospectively analyzed.
Result
Disease-causing variants were detected in all eight probands by molecular genetic analysis of the WS genes (SOX10(NM_006941.4): c.544_557del, c.553 C > T, c.762delA, c.336G > A; MITF(NM_000248.3): c.626 A > T; PAX3(NM_181459.4): c.838delG, c.452-2 A > G, c.214 A > G). Six mutations (SOX10:c.553 C > T, c.544_557del, c.762delA; PAX3: c.838delG, c.214 A > G; MITF:c.626 A > T) were first reported. Clinical evaluation revealed prominent phenotypic variability in these WS patients. Twelve WS1 cases and five WS2 cases were diagnosed in total. Two probands with SOX10 mutations developed progressive changes in iris color with age, returning from pale blue at birth to normal tan. Additionally, one proband had a renal malformation (horseshoe kidneys).All cases were first described as WS cases. Congenital inner ear malformations were more common, and semicircular malformations were exclusively observed in probands with SOX10 mutations. Unilateral hearing loss occurred more often in cases with PAX3 mutations.
Conclusion
Our findings helped illuminate the phenotypic and genotypic spectrum of WS in Chinese populations and could contribute to better genetic counseling of WS.
Funder
Hunan Province Natural Science Foundation
National Natural Science Foundation of China
China Postdoctoral Science Foundation
The science and technology innovation Program of Hunan Province China
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Cited by
2 articles.
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