Abstract
BackgroundWaardenburg syndrome (WS) is a dominantly inherited, genetically heterogeneous auditory‐pigmentary syndrome characterized by nonprogressive sensorineural hearing loss and iris discoloration. This study aimed to investigate the underlying molecular pathology in Chinese WS families.MethodsA total of 13 patients with Waardenburg syndrome type II (WS2) from six unrelated Chinese families were enrolled. We investigated the mutation profile of genes related to congenital deafness in these families through a targeted sequencing technology and validated the candidate variants by Sanger sequencing.ResultsWe identified six novel variants in microphthalmia‐associated transcription factor (MITF) and SRY‐box 10 (SOX10), which were predicted to be disease causing by in silico analysis. Our results showed that mutations in SOX10 and MITF are two major causes of deafness associated with WS, and de novo mutations were frequently found in probands with SOX10 mutations but not in those with MITF mutations.ConclusionResults showed that targeted next‐generation sequencing (NGS) enabled us to detect disease‐causing mutations with high accuracy, stability, speed and throughput. Our study extends the pathogenic mutation spectrum of MITF and SOX10.
Highlights
Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration
Many genes have been linked to WS, including paired box 3 (PAX3) (OMIM 606597), microphthalmia-associated transcription factor (MITF) (OMIM 156845), snail family zinc finger 2 (SNAI2) (OMIM 602150), endothelin receptor type B (EDNRB) (OMIM 131244), endothelin 3 (EDN3) (OMIM 131242), and SRY-box 10 (SOX10) (OMIM 602229)
Waardenburg syndrome, coined by Dutch ophthalmologist Petrus Johannes Waardenburg, is a neurocristopathy composed of hearing impairment and pigmentary abnormalities of eyes, skin and hair (Waardenburg, 1951)
Summary
Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration. Many genes have been linked to WS, including paired box 3 (PAX3) (OMIM 606597), MITF (OMIM 156845), snail family zinc finger 2 (SNAI2) (OMIM 602150), endothelin receptor type B (EDNRB) (OMIM 131244), endothelin 3 (EDN3) (OMIM 131242), and SOX10 (OMIM 602229). These genes are involved in the formation and development of several types of cells, including pigment-producing cells called melanocytes. We performed NGS to screen all possible genes associated with WS and congenital deafness simultaneously and identified six novel variants in MITF and SOX10 in patients. Our findings show that NGS can be a useful tool for the identification of pathogenic gene variants in WS patients
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