دورية أكاديمية
أعرض في EDS

Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases.

التفاصيل البيبلوغرافية
العنوان: Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases.
المؤلفون: Domínguez-Ruiz M; Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain., Olarte M; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá 110231, Colombia., Onecha E; Servicio de Genética, Hospital Universitario Marqués de Valdecilla, IDIVAL, 39008 Santander, Spain., García-Vaquero I; Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.; Programa de Doctorado en Biología, Escuela de Doctorado de la Universidad Autónoma de Madrid, 28049 Madrid, Spain., Gelvez N; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá 110231, Colombia., López G; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá 110231, Colombia., Villamar M; Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain., Morín M; Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain., Moreno-Pelayo MA; Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain., Morales-Angulo C; Servicio de Otorrinolaringología, Hospital Universitario Marqués de Valdecilla, IDIVAL, 39008 Santander, Spain.; Facultad de Medicina, Universidad de Cantabria, 39005 Santander, Spain., Polo R; Servicio de Otorrinolaringología, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain., Tamayo ML; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá 110231, Colombia., Del Castillo I; Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain.
المصدر: Genes [Genes (Basel)] 2024 Jul 19; Vol. 15 (7). Date of Electronic Publication: 2024 Jul 19.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel : MDPI
مواضيع طبية MeSH: Amino Acyl-tRNA Synthetases*/genetics, Humans ; Male ; Female ; Child ; Child, Preschool ; Adolescent ; Hearing Loss/genetics ; Mitochondrial Proteins/genetics ; Adult ; Pedigree ; Mitochondria/genetics ; Mutation ; Infant ; Deafness/genetics ; Phenotype ; Genetic Association Studies ; Lysine-tRNA Ligase/genetics
مستخلص: 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.
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معلومات مُعتمدة: PI20/00619 Instituto de Salud Carlos III; S2017/ BMD3721 Regional Government of Madrid; 00008286 Pontificia Universidad Javeriana
فهرسة مساهمة: Keywords: DFNB89; HARS2; KARS1; LARS2; Perrault syndrome; aminoacyl-tRNA synthetases; hearing loss; mitochondria
المشرفين على المادة: EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
EC 6.1.1.4 (LARS2 protein, human)
EC 6.1.1.21 (HARS2 protein, human)
0 (Mitochondrial Proteins)
EC 6.1.1.6 (Lysine-tRNA Ligase)
SCR Disease Name: Nonsyndromic Deafness
تواريخ الأحداث: Date Created: 20240727 Date Completed: 20240728 Latest Revision: 20240729
رمز التحديث: 20240729
مُعرف محوري في PubMed: PMC11276111
DOI: 10.3390/genes15070951
PMID: 39062730
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4425
DOI:10.3390/genes15070951