A novel mutation of the EYA1 gene in a branchio-otic syndrome child with secretory otitis media and bilateral vestibular weakness

AbstractObjective To investigate the phenotypic manifestations and molecular etiology of branchio-otic syndrome (BOS) in a Chinese family. Methods We recruited two generations of a Chinese family with BOS. Family history was obtained and detailed physical and hearing examinations were performed on all family members. Whole-exome sequencing (WES) was used to screen the candidate disease genes using phenolyzer software. Sanger sequencing was used for validation. The pathogenicity of the candidate mutations was analyzed. Results The proband had severe-to-profound sensorineural hearing loss in the left ear, and mixed hearing loss, type III cup-shaped ear, external auditory canal stenosis and cochlea hypoplasia in the right ear; Cochlear hypoplasia together with the fused lateral semicircular canal and vestibular in the left ear, with bilateral preauricular pits and branchial fistulae. Moreover, the patient had unilateral secretory otitis media(SOM) in the right ear and bilateral vestibular weakness (BVW), which has not been reported in previous studies. The patient’s hearing on the right side was restored to nearly normal after myringotomy with grommet insertion. We also identified a novel frameshift mutation in the proband (c.1697_1698delinsT[p.Lys566Ilefs*73]) in exon 17 of theEYA1gene, which was assessed as “pathogenic” according to American College of Medical Genetics and Genomics guidelines. Sanger sequencing was used to validate the novel heterozygous mutation and WES accuracy. Conclusion This is the first report of a child with BOS with SOM and BVW, further enriching the known phenotypes of this gene mutation. We also observed a novelEYA1gene mutation site in a patient with BOS, expanding the mutation map and providing a reference for genetic diagnosis.