Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment.
Mitochondrial mutations have previously been reported anecdotally in families with maternally inherited, nonsyndromic hearing impairment. To ascertain the contribution of mitochondrial mutations to postlingual but early-onset, nonsyndromic hearing impairment, we screened patients collected from within two different populations (southern Italy and UK) for previously reported mtDNA mutations associated with hearing disorders. Primer extension (SNP analysis) was used to screen for specific mutations, revealing cases of heteroplasmy and its extent. The most frequently implicated tRNA genes, Leu(UUR) and Ser(UCN), were also sequenced in all Italian patients. All tRNA genes were sequenced in those UK patients showing the clearest likelihood of maternal inheritance. Causative mtDNA mutations were found in approximately 5% of patients in both populations, representing almost 10% of cases that were clearly familial. Age of onset, where known, was generally before adulthood, and hearing loss was typically progressive. Haplogroup analysis revealed a possible excess of haplogroup cluster HV in the patients, compared with population controls, but of borderline statistical significance. In contrast, we did not find any of the previously reported mtDNA mutations, nor a significant deviation from haplogroup cluster frequencies typical of the control population, in patients with late adult-onset hearing loss (age-related hearing impairment) from the UK or Finland.
Institute of Medical Technology & Tampere University Hospital, Tampere, Finland. howard.t.jacobs@uta.fi
Howard T
HT
Jacobs
Timothy P
TP
Hutchin
Timo
T
Käppi
Greta
G
Gillies
Kia
K
Minkkinen
John
J
Walker
Karen
K
Thompson
Anja T
AT
Rovio
Massimo
M
Carella
Salvatore
S
Melchionda
Leopoldo
L
Zelante
Paolo
P
Gasparini
Ilmari
I
Pyykkö
Zahid H
ZH
Shah
Massimo
M
Zeviani
Robert F
RF
Mueller
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005387:Finland; D006239:Haplotypes / Q000235:genetics; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007558:Italy; D007806:Language Disorders / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D006113:United Kingdom
D004272:DNA, Mitochondrial