Abstract
Hearing impairment is the most frequent sensory defect in children, with a genetic basis in about 50% of cases. Several point mutations and deletions in mitochondrial DNA (mtDNA) have been identified in non-syndromic sensorineural hearing loss (NSSNHL). Beside the frequent A1555G mutation, a number of mutations in tRNAs have been reported recently, but their incidence remains unknown. We identified the T7511C mutation in the tRNASer(UCN) gene in two French families with isolated deafness. Maternal transmission was obvious in both. The 15 patients with hearing impairment exhibited a variable disease phenotype in terms of onset, severity, and progression. T7511C was present in all the patients screened. Homoplasmic and heteroplasmic levels were observed and did not correlate with the severity of the disease. T7511C was also present in 12 hearing offspring of the oldest deaf mothers, confirming the existence of modulatory factors. Our data suggest that this mtDNA mutation should be screened for in all cases of familial NSSNHL compatible with maternal transmission.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Petit C, Levilliers J, Hardelin JP . Molecular genetics of hearing loss Annu Rev Genet 2001 35: 589–645
Tamagawa Y, Kitamura K, Hagiwara H et al. Audiologic findings in patients with a point mutation at nucleotide 3243 of mitochondrial DNA Ann Otol Rhinol Laryngol 1997 106: 338–342
Ballinger SW, Shoffner JM, Hedaya EV et al. Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion Nat Genet 1992 1: 11–15
Servior KB, Hatamochi A, Stewart IA et al. Mitochondrial A7445G mutation in two pedigrees with palmoplantar keratoderma and deafness Am J Med Genet 1998 75: 179–185
Jaber L, Shohat M, Bu X et al. Sensorineural deafness inherited as a tissue specific mitochondrial disorder J Med Genet 1992 29: 86–90
Prezant TR, Agapian JV, Bohlman MC et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness Nat Genet 1993 4: 289–294
Casano RA, Johnson DF, Bykhovskaya Y, Torricelli F, Bigozzi M, Fischel-Ghodsian N . Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications Am J Otolaryngol 1999 20: 151–156
Estivill X, Govea N, Barcelo E et al. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides Am J Hum Genet 1998 62: 27–35
Hutchin TP, Parker MJ, Young ID et al. A novel mutation in the mitochondrial tRNA(Ser(UCN)) gene in a family with non-syndromic sensorineural hearing impairment J Med Genet 2000 37: 692–694
Sue CM, Tanji K, Hadjigeorgiou G et al. Maternally inherited hearing loss in a large kindred with a novel T7511C mutation in the mitochondrial DNA tRNA(Ser(UCN)) gene Neurology 1999 52: 1905–1908
Sternberg D, Danan C, Lombes A et al. Exhaustive scanning approach to screen all the mitochondrial tRNA genes for mutations and its application to the investigation of 35 independent patients with mitochondrial disorders Hum Mol Genet 1998 7: 33–42
Johnson KR, Zheng QY, Bykhovskaya Y, Spirina O, Fischel-Ghodsian N . A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice Nat Genet 2001 27: 191–194
Guan MX, Fischel-Ghodsian N, Attardi G . Biochemical evidence for nuclear gene involvement in phenotype of non- syndromic deafness associated with mitochondrial 12S rRNA mutation Hum Mol Genet 1996 5: 963–971
Guan MX, Fischel-Ghodsian N, Attardi G . Nuclear background determines biochemical phenotype in the deafness-associated mitochondrial 12S rRNA mutation Hum Mol Genet 2001 10: 573–580
Bykhovskaya Y, Yang H, Taylor K et al. Modifier locus for mitochondrial DNA disease: linkage and linkage disequilibrium mapping of a nuclear modifier gene for maternally inherited deafness Genet Med 2001 3: 177–180
Acknowledgements
This work was supported by the Fondation pour la Recherche Médicale, The Association Française contre les Myopathies, The Institut National de la Santé et de la Recherche Médicale, and The Association pour l'Etude de la Pathologie Pédiatrique.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chapiro, E., Feldmann, D., Denoyelle, F. et al. Two large French pedigrees with non syndromic sensorineural deafness and the mitochondrial DNA T7511C mutation: evidence for a modulatory factor. Eur J Hum Genet 10, 851–856 (2002). https://doi.org/10.1038/sj.ejhg.5200894
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5200894
Keywords
This article is cited by
-
Mitochondrial mutations in maternally inherited hearing loss
BMC Medical Genetics (2017)
-
Genetic etiology study of the non-syndromic deafness in Chinese Hans by targeted next-generation sequencing
Orphanet Journal of Rare Diseases (2013)
-
The Role of Mitochondrial DNA Mutations in Hearing Loss
Biochemical Genetics (2013)
-
The genetic bases for non-syndromic hearing loss among Chinese
Journal of Human Genetics (2009)
-
MRPS18CP2 alleles and DEFA3absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene
BMC Medical Genetics (2007)
