Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C→T mutation in the mitochondrial 12S rRNA gene

• Published in: Journal of medical genetics Vol. 43; no. 11; p. e54
• Main Authors: Rodríguez-Ballesteros, M, Olarte, M, Aguirre, L A, Galán, F, Galán, R, Vallejo, L A, Navas, C, Villamar, M, Moreno-Pelayo, M A, Moreno, F, del Castillo, I
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.11.2006; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adult; Age of Onset; Aged; Aminoglycosides - therapeutic use; Anti-Bacterial Agents - therapeutic use; Antibiotics; Child; Ethnicity; Female; Genes; Genes, Mitochondrial; Genetic Testing; Hearing loss; Hearing Loss, Bilateral - diagnosis; Hearing Loss, Bilateral - drug therapy; Hearing Loss, Bilateral - genetics; Hearing Loss, Sensorineural - diagnosis; Hearing Loss, Sensorineural - drug therapy; Hearing Loss, Sensorineural - genetics; Hearing protection; Humans; Inheritance Patterns; lactic acidosis and stroke-like episodes; Male; maternally inherited diabetes mellitus and deafness; MELAS; MERRF; MIDD; Middle Aged; Mitochondrial DNA; mitochondrial encephalomyopathy; mtDNA; Mutation; myoclonus epilepsy and ragged-red fibres; non-syndromic hearing loss; NSHL; Online Mutation Report; Patients; PCR; Pedigree; Point Mutation; Polymerase chain reaction; rCRS; revised Cambridge reference sequence; RNA, Ribosomal - chemistry; RNA, Ribosomal - genetics; Sequence Analysis, DNA; Spain; Transfer RNA; Spain
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2006.042440

Mutations in the 12S rRNA gene of the mitochondrial genome are responsible for maternally inherited non-syndromic hearing loss (NSHL), and for increased susceptibility to the ototoxicity of aminoglycoside antibiotics. Among these mutations, 1555A→G is the most prevalent in all populations tested so far. Recently, the 1494C→T mutation was reported in two large Chinese pedigrees with maternally inherited NSHL. In this study, sequencing of the 12S rRNA gene in a Spanish family with maternally inherited NSHL showed the presence of the 1494C→T mutation. An additional screening of 1339 unrelated Spanish patients with NSHL allowed the authors to find two other families with the mutation. Audiological data were obtained from 17 confirmed 1494C→T carriers, which showed that the hearing loss was sensorineural, bilateral and symmetrical, with a remarkable variability in age of onset and severity. Three carriers were asymptomatic. Three affected carriers had a history of treatment with aminoglycoside antibiotics. The mitochondrial genome of one affected person from each of these three families was entirely sequenced, and it was established that they belong to different mitochondrial haplogroups (H, U5b, U6a). The study results further support the pathogenic role of 1494C→T on hearing, and show that this mutation can be found in different Caucasian mitochondrial DNA backgrounds.