[Nonsyndromic inherited hearing impairment caused by mtDNA double mutations of A1555G and 961 insC].
OBJECTIVE
To investigate the genotypes of mitochondrial DNA mutations of a large nonsyndromic inherited hearing impairment pedigree.


METHODS
The diagnosis was validated by hearing test. Blood samples from the branch pedigree (33 members) and 6 sporadic patients were obtained. DNA was extracted from the leukocytes. The mitochondrial DNA target fragments were amplified by polymerase chain reaction(PCR). The 1555G, 3243G and 7445G mutations were detected by BsmA I, Apa I and Xba I restriction endonuclease digestion respectively. Some PCR products were analyzed by sequencing.


RESULTS
Restriction endonuclease digestion identified that 17 patients from the pedigree carried 1555G mutation. All pedigree members, including patients and sporadic patients, did not have 3243G and 7445G mutation. In 6 patients of the pedigree DNA sequence analysis revealed double mutations, an A>G transition at position 1555 and a C insertion at position 961, whereas the unaffected relatives of the pedigree and sporadic patients did not have such mutations. None of them carried 3243G and 7445G mutation.


CONCLUSIONS
Double mutations of A1555G and 961 insC in mitochondrial DNA 12S rRNA gene region may play a pivotal role in the pathogenesis of hearing loss in the large nonsyndromic inherited hearing impairment pedigree.
Cao
Xin
X
Department of Cell Biology and Medical Genetics, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210029 P. R. China.
Xing
Guang-qian
GQ
Wei
Qin-jun
QJ
Bu
Xing-kuan
XK
Wang
Deng-yuan
DY
D001483:Base Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D034381:Hearing Loss / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional; D010375:Pedigree; D017354:Point Mutation
D004272:DNA, Mitochondrial