title: SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss.
abstract: Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with postlingual non-syndromic mid-frequency sensorineural hearing loss. Whole-exome sequencing revealed SLC44A4, which encodes the choline transport protein, as the pathogenic gene in this family. In the zebrafish model, downregulation of slc44a4 using morpholinos led to significant abnormalities in the zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance. SH-SY5Y cells transfected with SLC44A4 showed higher choline uptake and acetylcholine release than that of cells transfected with mutant SLC44A4. We concluded that mutation of SLC44A4 may cause defects in the Choline- acetylcholine system, which is crucial to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury, leading to hearing loss.
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200120, People's Republic of China.
authors.forename: Zhaoxin
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Institute of Biomedical Science, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xia
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China and.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China and.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China and.
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China and.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China and.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China and.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200120, People's Republic of China.
authors.forename: Jiongjiong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute of Biomedical Science, Fudan University, Shanghai, 200032, People's Republic of China.|Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, Collaborative Innovation Center of Genetics and Development, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China and.|Children's Hospital, Fudan University, 200032, People's Republic of China.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D044466:Asian People; D007758:Ear, Inner / Q000503:physiopathology*; D059472:Exome / Q000235:genetics; D056726:Genetic Association Studies; D006198:Hair Cells, Auditory / Q000473:pathology; D034381:Hearing Loss / Q000235:genetics* / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D060172:Morpholinos; D009154:Mutation; D010375:Pedigree; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development
chemical_list: D026901:Membrane Transport Proteins; D060172:Morpholinos; C583905:SLC44A4 protein, human