Correspondence
Prevalence of Mitochondrial 1555A→G Mutation in Adults of European Descent
N Engl J Med 2009; 360:642-644February 5, 2009
- Article
To the Editor:
Sensorineural hearing loss is the most common type of sensory impairment worldwide.1 We have found that pathogenic mitochondrial DNA (mtDNA) mutations, such as the m.3243A→G mutation associated with mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS), are prevalent and can cause sensorineural hearing loss in adults of European descent.2 Polymorphisms within mtDNA can modify a patient's risk of hearing loss.3 The m.1555A→G mutation, which is located in the 12S ribosomal RNA gene of the mitochondrial genome, is known to cause hearing loss, especially after exposure to aminoglycoside antibiotics.4
We prospectively collected audiologic data and DNA from blood and hair-follicle samples from 2856 subjects over the age of 49 years who were noninstitutionalized permanent residents of two suburban areas west of Sydney (known as the Blue Mountains Hearing Study cohort)2 and screened them for the m.1555A→G mutation, using polymerase-chain-reaction–restriction-fragment–length polymorphism techniques. We also carried out mitochondrial DNA haplogroup analysis (for details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org).
Of the 2856 subjects, 6 had homoplasmic m.1555A→G mutations, providing a population prevalence of 0.21% (95% confidence interval, 0.08 to 0.46). According to family history obtained by interview, none of the mutation carriers were related to one another, either genetically or by marriage. Two of them belonged to mtDNA haplogroup U, two to mtDNA haplogroup J, and one to mtDNA haplogroup H. The haplotype on which the mutation of the sixth carrier occurred could not be determined. All six carriers had audiologic evidence of sensorineural hearing loss in at least one ear (Figure 1Figure 1
Mean Auditory Thresholds for Six Subjects with the m.1555A→G Mutation, as Compared with Predicted Thresholds., and tables in the Supplementary Appendix). All carriers reported having had no exposure to aminoglycosides.We performed multiple linear regression analysis with adjustment for age, sex, and other risk factors for hearing loss, such as a family history of hearing loss, occupational noise exposure, and a history of type 2 diabetes. Mean auditory thresholds were calculated for each ear, given that two mutation carriers had asymmetrical hearing loss, a feature typical of mitochondrial hearing loss.5 After adjustment for these variables, mean auditory thresholds were significantly higher in three of the six carriers than in the general population (Figure 1, and the Supplementary Appendix). The subject who was exposed to ototoxic drugs (quinine and furosemide) had the earliest age of onset (58 years) and the longest duration of hearing loss (>20 years).
We conclude that the m.1555A→G mutation affects about 1 in 500 subjects in our population-based cohort and independently causes sensorineural hearing loss. The population prevalence of the m.1555A→G mutation in our sample is nearly identical to that reported in this issue of the Journal in a letter by Bitner-Glindzicz et al.,6 who genotyped British children of European descent. The population prevalence of the m.1555A→G mutation is similar to that of the MELAS m.3243A→G mutation,2 for a combined prevalence of about 1 in 250. These data indicate that mtDNA mutations may be a common genetic cause of sensorineural hearing loss in persons of European descent.
Himesha Vandebona, Ph.D.
University of Sydney Kolling Institute for Medical Research, Sydney, NSW 2065, AustraliaPaul Mitchell, M.D., Ph.D.
University of Sydney Centre for Vision Research, Sydney, NSW 2145, AustraliaNeil Manwaring, Ph.D.
Kate Griffiths, B.Sc.
University of Sydney Kolling Institute for Medical Research, Sydney, NSW 2065, AustraliaBamini Gopinath, Ph.D.
Jie Jin Wang, M.Med., Ph.D.
University of Sydney Centre for Vision Research, Sydney, NSW 2145, AustraliaCarolyn M. Sue, M.B., B.S., Ph.D.
University of Sydney Kolling Institute for Medical Research, Sydney, NSW 2065, Australia
csue@med.usyd. edu. au Supported by grants (302166, 975159, 991047, and 211069) from the Australian National Health and Medical Research Council and the Australian Brain Foundation.
Dr. Mitchell reports receiving consulting fees from Novartis, Pfizer, and Solvay Pharmaceuticals, lecture fees from Novartis and Solvay Pharmaceuticals, and grant support from Pfizer. No other potential conflict of interest relevant to this letter was reported.
6 References1
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Bitner-Glindzicz M ,Pembrey M ,Duncan A , et al. Prevalence of mitochondrial 1555A→G mutation in European children. N Engl J Med 2009;360:640-642
Full Text | Web of Science | Medline
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