{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:54:24Z","timestamp":1787237664711,"version":"build-2736575974"},"reference-count":16,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2021,8]]},"abstract":"\n Background:<\/jats:title>\n \n Variants in the\n HARS2<\/jats:italic>\n gene have been reported to be associated with nonsyndromic hearing loss (HL) and Perrault syndrome (PS), a rare recessive disorder marked by bilateral sensorineural HL and ovarian dysgenesis. Given the low number of pathogenic variants described in the\n HARS2<\/jats:italic>\n gene, no genotype\/phenotype correlations have been established between variants in this gene and the clinical data.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n Whole blood was collected from four members of a Lebanese family with PS. An affected woman was evaluated for HL by clinical examination and audiological tests. Primary ovarian failure was analyzed according to age of primary or secondary amenorrhea, follicle stimulating hormone levels, and pelvic ultrasound. The existence of neurological symptoms and other associated conditions was checked. To identify the causative variant, we used a custom HaloPlex\n HS<\/jats:sup>\n panel for next-generation sequencing of the coding sequences of six genes implicated in this syndrome.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n We identified a novel homozygous\n HARS2<\/jats:italic>\n missense variant (c.260G>A;\n p.Arg87His<\/jats:ext-link>\n ), which is only the second homozygous variant in the\n HARS2<\/jats:italic>\n gene identified to date worldwide. This variant is predicted to be deleterious by multiple\n in silico<\/jats:italic>\n analysis tools, moreover the Arg87 amino acid nearly is invariant among eight species. Based on molecular modeling analysis, this variation is predicted to disturb the proper folding of HARS2, which may reduce its aminoacylation efficiency. Clinical data are compared with the other cases recorded in the literature to help gain further knowledge with regard to the phenotype.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Our results provide strong evidence corroborating the etiological association of this mutation with the HARS2-PS phenotype.\n HARS2<\/jats:italic>\n variants need to be searched for in patients with early-onset bilateral sensorineural HL and ovarian dysfunction in women so as to guarantee accurate endocrinological surveillance and management to minimize secondary complications.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/gtmb.2021.0092","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T16:47:42Z","timestamp":1629305262000},"page":"528-539","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Expanding the Clinical and Molecular Spectrum of HARS2-Perrault Syndrome: Identification of a Novel Homozygous Missense Variant in the\n HARS2<\/i>\n gene"],"prefix":"10.1177","volume":"25","author":[{"given":"Amal","family":"Souissi","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-4537","authenticated-orcid":false,"given":"Mariem","family":"Ben Said","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakher","family":"Frikha","sequence":"additional","affiliation":[{"name":"Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Elloumi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saber","family":"Masmoudi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Megarbane","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2015.04.038"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2019.1637407"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12776"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0706-1"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-2041-x"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.103733"},{"key":"e_1_3_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23120"},{"key":"e_1_3_5_9_1","volume-title":"Gene Reviews","author":"Newman WG","year":"1993","unstructured":"Newman WG, , Friedman TB, , Conway GS, et al. (1993) Perrault Syndrome. Gene Reviews. University of Washington, Seattle (WA)."},{"key":"e_1_3_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103471108"},{"key":"e_1_3_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.03.007"},{"key":"e_1_3_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.01.005"},{"key":"e_1_3_5_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/14992027.2017.1281444"},{"key":"e_1_3_5_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41065-020-00157-7"},{"key":"e_1_3_5_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000198"},{"key":"e_1_3_5_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13638"}],"container-title":["Genetic Testing and Molecular Biomarkers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/gtmb.2021.0092","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/gtmb.2021.0092","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/gtmb.2021.0092","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:23:05Z","timestamp":1777447385000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/gtmb.2021.0092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":16,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1089\/gtmb.2021.0092"],"URL":"https:\/\/doi.org\/10.1089\/gtmb.2021.0092","relation":{},"ISSN":["1945-0265","1945-0257"],"issn-type":[{"value":"1945-0265","type":"print"},{"value":"1945-0257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8]]}}}