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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
  1. M Rodríguez-Ballesteros1,*,
  2. M Olarte1,*,
  3. L A Aguirre1,
  4. F Galán2,
  5. R Galán2,
  6. L A Vallejo3,
  7. C Navas4,
  8. M Villamar5,
  9. M A Moreno-Pelayo5,
  10. F Moreno5,
  11. I del Castillo5
  1. 1Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid, Spain
  2. 2Departamento de Pediatría, Facultad de Medicina, Universidad Miguel Hernández, Alicante, Spain
  3. 3Servicio de ORL, Hospital Río Hortega, Valladolid, Spain
  4. 4Servicio de ORL, Hospital Ramón y Cajal, Madrid, Spain
  5. 5Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid, Spain
  1. Correspondence to:
 I del Castillo
 Unidad de Genética Molecular, Hospital Ramón y Cajal, Carretera de Colmenar, Km 9, 28034 Madrid, Spain; idelcastillo.hrc{at}salud.madrid.org

Abstract

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.

  • rCRS, revised Cambridge reference sequence
  • MELAS, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
  • MERRF, myoclonus epilepsy and ragged-red fibres
  • MIDD, maternally inherited diabetes mellitus and deafness
  • mtDNA, mitochondrial DNA
  • NSHL, non-syndromic hearing loss
  • PCR, polymerase chain reaction

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Footnotes

  • * These authors contributed equally to this work.

  • Funding: This work was supported by grants from the European Commission (FP6 Integrated Project EUROHEAR, LSHG-CT-2004-512063), Ministerio de Ciencia y Tecnología (SAF2002-03966), Red Tau (Spanish Research Network on the Genetic and Molecular Bases of Hearing Disorders, FIS G03/203), Programa Ramón y Cajal (to IdC), Fondo de Investigaciones Sanitarias (FIS PI020807) and Fundación Ramón Areces.

  • Competing interests: None.

  • MRB, MO and LAA were recipients of fellowships from Fondo de Investigaciones Sanitarias, Fundación Carolina, and Fundación ONCE (Organización Nacional de Ciegos Españoles), respectively.

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