New role of LRP5, associated with nonsyndromic autosomal‐recessive hereditary hearing loss |
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| Authors: | Fei Liu Jing Ma Shaoyang Sun Jin Zhang Kaiyue Jin Jianbo Huang Nan Jiang Xu Wang Wen Li Zhaoxin Ma Duan Ma |
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| Affiliation: | 1. 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, China;2. Center Laboratory, Bao'an Maternal and Children Healthcare Hospital, Key Laboratory of Birth Defects Research, Shenzhen, China;3. Eye & ENT Hospital, Fudan University, Shanghai, China;4. Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, China;5. Institutes of Biomedical Science, Fudan University, Shanghai, China;6. Children's Hospital, Fudan University, Shanghai, China |
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| Abstract: | Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. At least 50% of hearing loss are due to a genetic etiology. Although hundreds of genes have been reported, there are still hundreds of related deafness genes to be found. Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with postlingual nonsyndromic sensorineural hearing loss. Whole‐exome sequencing (WES) identified lipoprotein receptor‐related protein 5 (LRP5), a member of the low‐density lipoprotein receptor family, as the causative gene in this family. In the zebrafish model, lrp5 downregulation using morpholinos led to significant abnormalities in zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance. Rescue experiments showed that LRP5 mutation is associated with hearing loss. Knocking down lrp5 in zebrafish results in reduced expression of several genes linked to Wnt signaling pathway and decreased cell proliferation when compared with those in wild‐type zebrafish. In conclusion, the LRP5 mutation influences cell proliferation through the Wnt signaling pathway, thereby reducing the number of supporting cells and hair cells and leading to nonsyndromic hearing loss in this Chinese family. |
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| Keywords: | hereditary hearing loss LRP5 nonsyndromic hearing loss Wnt signaling pathway |
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