Abstract
Waardenburg syndrome (WS), also known as auditory-pigmentary syndrome, is the most common cause of syndromic hearing loss. It is responsible for 2–5% of congenital deafness. WS is classified into four types depending on the clinical phenotypes. Currently, pathogenic mutation of PAX3, MITF, EDNRB, EDN3, SNAI2, or SOX10 can cause corresponding types of WS. Among them, SOX10 mutation is responsible for approximately 15% of type II WS or 50% of type IV WS. We report the case of a proband in a Chinese family who was diagnosed with WS type II. Whole exome sequencing (WES) of the proband detected a novel heterozygous spontaneous mutation: SOX10 c.246delC. According to analysis based on nucleic acid and amino acid sequences, this mutation may produce a truncated protein, with loss of the HMG structure domain. Therefore, this truncated protein may fail to activate the expression of the MITF gene, which regulates melanocytic development and plays a key role in WS. Our finding expands the database of SOX10 mutations associated with WS and provides more information regarding the molecular mechanism of WS.
Highlights
Waardenburg syndrome (WS), known as auditorypigmentary syndrome, is one of the most common causes of syndromic deafness, associated with 2–5% of congenital deafness cases [1]
The audiology examination of the proband showed failed bilateral otoacoustic emissions; all bilateral auditory brainstem response (ABR) thresholds were over 105 dB nHL; auditory steady-state evoked responses (ASSR) showed the thresholds of the left ear were 105 dB nHL at 1 kHz, 105 dB nHL at 2 kHz, and 90 dB nHL at 4 kHz, while the thresholds of the right ear were 90 dB nHL at 500 Hz, 105 dB nHL at 1 kHz, and 100 dB nHL at 4 kHz (Figures 2(a) and 2(b))
The temporal bone computed tomography (CT) scan suggested that the shape and size of the bilateral cochleae were not obviously abnormal; the middle and top circles of the cochleae were obscurely decomposed, the vestibule was slightly enlarged on both sides, all the right semicircular canals were fused with the vestibule, the left posterior and superior semicircular canals were short, and the horizontal semicircular canal was fused with the vestibule (Figures 2(c) and 2(d))
Summary
Waardenburg syndrome (WS), known as auditorypigmentary syndrome, is one of the most common causes of syndromic deafness, associated with 2–5% of congenital deafness cases [1]. Basic clinical symptoms of WS include dystopia of the canthus; abnormal pigmentation of the skin, hair, and eyes; different degrees of unilateral or bilateral sensorineural deafness; and a high and wide nasal base. The clinical manifestations of type II are basically the same as type I, but without dystopia of the canthus. The clinical manifestations of type III are the same as type I, but combined with upper limb deformity, while type IV exhibits basically the same symptoms as type II, but combined with Hirschsprung disease (gastrointestinal malformation) [3,4,5,6]. SOX10 mutations cause approximately 15% of type II WS and 45–55% of type IV WS [9, 10]. The total number of reported SOX10 pathogenic mutations related to WS is 82, according to the Leiden Open Variation Database (LOVD) (https://grenada.lumc.nl/LOVD2/WS/home)
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