@article{10902/34461,
year = {2024},
url = {https://hdl.handle.net/10902/34461},
abstract = {Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of roles that are played by these moonlighting enzymes and the fact that most pathogenic variants are missense and affect different domains of these proteins in diverse compound heterozygous combinations make it difficult to establish genotype?phenotype correlations. We used a targeted gene-sequencing panel to investigate the presence of pathogenic variants in those four genes in cohorts of 175 Spanish and 18 Colombian familial cases with non-DFNB1 autosomal recessive NSHI. Disease-associated variants were found in five cases. Five mutations were novel as follows: c.766C>T in KARS1, c.475C>T, c.728A>C and c.1012G>A in HARS2, and c.795A>G in LARS2. We provide audiograms from patients at different ages to document the evolution of the hearing loss, which is mostly prelingual and progresses from moderate/severe to profound, the middle frequencies being more severely affected. No additional clinical sign was observed in any affected subject. Our results confirm the involvement of KARS1 in DFNB89 NSHI, for which until now there was limited evidence.},
organization = {Funding: This research was funded by the Instituto de Salud Carlos III (ISCIII), Madrid, Spain, National Plan for Scientific and Technical Research and Innovation 2017–2020, with cofunding from the European Regional Development Fund, “A way to make Europe”, grant number PI20/00619 (to I.d.C.); by the Regional Government of Madrid, grant number S2017/BMD3721 (to M.A.M-P.); and by the Vicerrectoría de Investigación of Pontificia Universidad Javeriana of Bogotá (ID number 00008286) (to M.L.T.).
Acknowledgments: We kindly thank the patients and their relatives who participated in this study.},
publisher = {MDPI},
publisher = {Genes, 2024, 15,
 951},
title = {Novel cases of non-syndromic hearing impairment caused by pathogenic variants in genes encoding mitochondrial aminoacyl-tRNA synthetases},
author = {Domínguez-Ruiz, María and Olarte, Margarita and Onecha de la Fuente, María Esther and García-Vaquero, Irene and Gelvez, Nancy and López, Greizy and Villamar, Manuel and Morín, Matías and Moreno-Pelayo, Miguel A. and Morales Angulo, Carmelo and Polo, Rubén and Tamayo, Martha L. and Castillo, Ignacio del},
}