{"doi":"10.1101/2020.06.29.178053","title":"Homozygote loss-of-function variants in the human <i>COCH</i> gene underlie hearing loss","abstract":"Abstract Since 1999, the COCH gene encoding cochlin, has been linked to the autosomal dominant non-syndromic hearing loss, DFNA9, with or without vestibular abnormalities. The hearing impairment associated with the variants affecting gene function has been attributed to a dominant-negative effect. Mutant cochlin was seen to accumulate intracellularly, with the formation of aggregates both inside and outside the cells, in contrast to the wild-type cochlin that is normally secreted. While an additional recessive variant in the COCH gene (DFNB110) has recently been reported, the mechanism of the loss-of-function (LOF) effect of the COCH gene product remains unknown. In this study, we used COS7 cell lines to investigate the consequences of a novel homozygous frameshift variant on RNA transcription, and on cochlin translation. Our results indicate a LOF effect of the variant and a major decrease in cochlin translation. This data has a dramatic impact on the accuracy of genetic counseling for both heterozygote and homozygote carriers of LOF variants in COCH .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":127019,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":431266,"name":"Elena Chervinsky","orcid":null,"position":1,"is_corresponding":false},{"id":430265,"name":"Prathamesh T. Nadar‐Ponniah","orcid":"0000-0002-1087-9069","position":2,"is_corresponding":false},{"id":430266,"name":"Eran Cohen‐Barak","orcid":"0000-0002-5454-7242","position":3,"is_corresponding":false},{"id":377170,"name":"Shahar Taiber","orcid":"0000-0002-0787-4216","position":4,"is_corresponding":false},{"id":430267,"name":"Morad Khayat","orcid":"0000-0002-4817-7492","position":5,"is_corresponding":false},{"id":377172,"name":"Karen B. Avraham","orcid":"0000-0002-4913-251X","position":6,"is_corresponding":false},{"id":575105,"name":"Stavit A. Shalev","orcid":"0000-0002-0414-3450","position":7,"is_corresponding":false},{"id":430264,"name":"Nada Danial‐Farran","orcid":"0000-0001-8092-3144","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}