LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss.

Autor: Neyroud AS; CHU Rennes, Service de Biologie de la Reproduction-CECOS, F-35033, Rennes, France.; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, F-35000, Rennes, France., Rudinger-Thirion J; Université de Strasbourg, Architecture et Réactivité de l'ARN, CNRS, IBMC, Strasbourg, France., Frugier M; Université de Strasbourg, Architecture et Réactivité de l'ARN, CNRS, IBMC, Strasbourg, France., Riley LG; Rare Diseases Functional Genomics, Kids Research, The Children's Hospital at Westmead and The Children's Medical Research Institute, Sydney, NSW, Australia.; Specialty of Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Bidet M; Clinique Mutualiste La Sagesse, Service of AMP, 35000, Rennes, France., Akloul L; CHU Rennes, Service de Génétique Clinique, CLAD Ouest, F-35033, Rennes, France., Simpson A; School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC, Australia.; College of Health and Human Services, Charles Darwin University, Darwin, NT, Australia., Gilot D; CHU Rennes, Service de Cytogénétique et Biologie Cellulaire, F-35033, Rennes, France.; INSERM U1242, COSS, Université Rennes 1, F-35032, Rennes, France., Christodoulou J; Specialty of Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia., Ravel C; CHU Rennes, Service de Biologie de la Reproduction-CECOS, F-35033, Rennes, France.; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, F-35000, Rennes, France., Sinclair AH; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia., Belaud-Rotureau MA; CHU Rennes, Service de Biologie de la Reproduction-CECOS, F-35033, Rennes, France.; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, F-35000, Rennes, France.; School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC, Australia., Tucker EJ; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia. elena.tucker@mcri.edu.au.; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia. elena.tucker@mcri.edu.au., Jaillard S; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, F-35000, Rennes, France. sylvie.jaillard@chu-rennes.fr.; CHU Rennes, Service de Cytogénétique et Biologie Cellulaire, F-35033, Rennes, France. sylvie.jaillard@chu-rennes.fr.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2023 Apr; Vol. 31 (4), pp. 453-460. Date of Electronic Publication: 2022 Dec 01.
DOI: 10.1038/s41431-022-01252-1
Abstrakt: Premature ovarian insufficiency (POI) affects 1 in 100 women and is a leading cause of female infertility. There are over 80 genes in which variants can cause POI, with these explaining only a minority of cases. Whole exome sequencing (WES) can be a useful tool for POI patient management, allowing clinical care to be personalized to underlying cause. We performed WES to investigate two French sisters, whose only clinical complaint was POI. Surprisingly, they shared one known and one novel likely pathogenic variant in the Perrault syndrome gene, LARS2. Using amino-acylation studies, we established that the novel missense variant significantly impairs LARS2 function. Perrault syndrome is characterized by sensorineural hearing loss in addition to POI. This molecular diagnosis alerted the sisters to the significance of their difficulty in following conversation. Subsequent audiology assessment revealed a mild bilateral hearing loss. We describe the first cases presenting with perceived isolated POI and causative variants in a Perrault syndrome gene. Our study expands the phenotypic spectrum associated with LARS2 variants and highlights the clinical benefit of having a genetic diagnosis, with prediction of potential co-morbidity and prompt and appropriate medical care, in this case by an audiologist for early detection of hearing loss.
(© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)
Databáze: MEDLINE
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