Two large French pedigrees with non syndromic sensorineural deafness and the mitochondrial DNA T7511C mutation: evidence for a modulatory factor.
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.
Chapiro
Elise
E
Service de biochimie et de biologie moléculaire, Hôpital d'Enfants Armand-Trousseau, AP-HP, Paris, France.
Feldmann
Delphine
D
Denoyelle
Françoise
F
Sternberg
Damien
D
Jardel
Claude
C
Eliot
Marie-Madeleine
MM
Bouccara
Didier
D
Weil
Dominique
D
Garabédian
Eréa-Noel
EN
Couderc
Rémy
R
Petit
Christine
C
Marlin
Sandrine
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005602:France; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D004272:DNA, Mitochondrial