Audio profiles in mitochondrial deafness m.1555A>G and m.3243A>G show distinct differences.
BACKGROUND
Hearing loss is one of the most common symptoms of mitochondrial disorders. However, audiological phenotypes associated with different molecular defects in mtDNA are not yet well characterized.


METHODS
A large cohort of 1499 nonconsanguineous patients aged 5-40 years with hearing loss of unknown etiology was screened for mutations in mtDNA. For further analysis, patients harboring m.1555A>G and m.3243A>G were selected. Hearing status of the patients was assessed by pure tone audiometry. Patterns of audiograms (hearing threshold levels at each examined frequency) were statistically compared among the carriers of the m.1555A>G and the m.3243A>G mutations.


RESULTS
We identified 20 patients positive for m.1555A>G mutation and 16 patients positive for m.3243A>G change. The frequency of the above transitions was calculated in our cohort as 1.33% and 1.06%, respectively. Seventeen affected family members carrying the mutations were included into the study. Typical shape of the audiograms in patients with m.1555A>G mutation presented a ski-slope pattern, whereas the audiometric curves among the m.3243A>G individuals had a pantonal shape (a flat curve) with slight downward sloping at the higher frequencies. The differences were statistically significant. The onset of hearing loss was noted earlier among m.1555A>G than m.3243A>G patients (12.5 and 26 years, respectively). Aminoglycoside administration was declared in both groups in 11 and 4 cases respectively, and caused abrupt hearing deterioration in all cases.


CONCLUSIONS
A pattern of audiogram in patients with mitochondrial deafness may suggest a localization of mtDNA mutation. The pathogenesis of the audiometric differences needs further study.
Department of Audiology Phoniatrics and Laryngology, Children's Memorial Health Institute, Warsaw, Poland.
Katarzyna
K
Iwanicka-Pronicka
Department of Genetics, Institut of Physiology and Pathology of Hearing, Kajetany/Warsaw, Poland.
Agnieszka
A
Pollak
Department of Pediatrics, Warsaw Medical University, Warsaw, Poland.
Agata
A
Skórka
Department of Genetics, Institut of Physiology and Pathology of Hearing, Kajetany/Warsaw, Poland.
Urszula
U
Lechowicz
Department of Genetics, Institut of Physiology and Pathology of Hearing, Kajetany/Warsaw, Poland.
Lech
L
Korniszewski
Department of Administration, Children's Memorial Health Institute, Warsaw, Poland.
Przemysław
P
Westfal
Department of Otorhinolaryngology, Institute of Physiology and Pathology of Hearing, Kajetany/Warsaw, Poland.
Henryk
H
Skarżyński
Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
Rafał
R
Płoski
D000293:Adolescent; D000328:Adult; D001299:Audiometry; D001309:Auditory Threshold; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D034381:Hearing Loss; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D055815:Young Adult
D004272:DNA, Mitochondrial