title: High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder.
abstract: Auditory neuropathy spectrum disorder (ANSD) is one of the most common diseases leading to hearing and speech communication barriers in infants and young children. The OTOF gene is the first gene identified for autosomal recessive non-syndromic ANSD, and patients with OTOF mutations have shown marked improvement of auditory functions from the cochlear implantation, but the true involvement of OTOF mutations in Chinese ANSD patients is still unknown which precludes the effective management of this disease. Here, we investigated the contribution of OTOF mutations to congenital ANSD patients in China. In all, 37 infants and young Children with ANSD were screened for all the exons of OTOF gene, of them 34 patients had no neonatal risk factors who were considered as congenital ANSD. The clinical manifestation and audiometric features were also investigated and compared in patients with and without OTOF mutations. In all, 14 of these subjects were shown to carry two or three mutant alleles of OTOF with the high frequency of 41.2% in congenital ANSD patients. In total, 15 novel pathogenic mutations and 10 reported mutations were identified. Our results confirmed that mutations in OTOF gene were a major cause of congenital ANSD in China. Identification of OTOF mutations can facilitate diagnosis, clinical intervention and counseling for congenital ANSD.
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Q-J
authors.initials: QJ
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Zong
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Z-F
authors.initials: ZF
authors.lastname: Yin
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: D-Y
authors.initials: DY
authors.lastname: Wang
authors.affiliation: Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Collège de France, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Petit
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Otolaryngology/ Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Q-J
authors.initials: QJ
authors.lastname: Wang
mesh_terms: D000483:Alleles; D001299:Audiometry; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D006311:Hearing Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D006313:Hearing Loss, Central / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation
chemical_list: D008565:Membrane Proteins; C118457:OTOF protein, human
keywords: OTOF; auditory neuropathy; auditory neuropathy spectrum disorder; hearing impairment; otoferlin