2. Academic Validation
  3. SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss

SLC44A4 mutation causes autosomal dominant hereditary postlingual non-syndromic mid-frequency hearing loss

  • Hum Mol Genet. 2017 Jan 15;26(2):383-394. doi: 10.1093/hmg/ddw394.
Zhaoxin Ma 1,  Wenjun Xia 2,  Fei Liu 3,  Jing Ma 3,  Shaoyang Sun 3,  Jin Zhang 3,  Nan Jiang 3,  Xu Wang 3,  Jiongjiong Hu 1,  Duan Ma 2 3 4
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200120, People's Republic of China.
  • 2 Institute of Biomedical Science, Fudan University, Shanghai, 200032, People's Republic of China.
  • 3 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.
  • 4 Children's Hospital, Fudan University, 200032, People's Republic of China.
PMID: 28013291 DOI: 10.1093/hmg/ddw394
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.

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