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Identification of eight novel variants across PAX3, SOX10, EDNRB and MITF genes in Waardenburg syndrome with next-generation sequencing

Lee, C.-Y.; Lo, M.-Y.; Chen, Y.-M.; Lin, P.-H.; Hsu, C.-J.; Chen, P.-L.; Wu, C.-C.; Hsu, J. S.-j.

2022-01-27 otolaryngology
10.1101/2022.01.18.21267034 medRxiv
Show abstract

Waardenburg syndrome (WS) is a hereditary, genetically heterogeneous disorder characterized by variable presentations of sensorineural hearing impairment and pigmentation anomalies. This study aimed to investigate the clinical features of WS in detail and determine the genetic causes of patients with clinically suspected WS. A total of 24 patients from 21 Han Taiwanese families were enrolled and underwent comprehensive physical and audiological examination. We applied targeted next-generation sequencing (NGS) to investigate the potential causative variants in these patients and further validated the candidate variants through Sanger sequencing. We identified 18 causative variants of WS in our cohort. Of these variants, eight were novel and discovered in PAX3, SOX10, EDNRB, MITF genes, including missense, nonsense, deletion, and splice site variants. Several patients presented skeletal deformities, hypotonia, megacolon, and neurological disorders that were rarely seen in WS. This study revealed highly phenotypic variability in Taiwanese WS patients and demonstrated that targeted NGS allowed us to clarify the genetic diagnosis and extend the genetic variant spectrum of WS.

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