OBJECTIVETo investigate the genetic mechanism of maternal nonsyndromic inherited sensorineural hearing loss(SNHL), to identify the incidence of the 7445(G) mutation in such pedigrees and sporadic patients with SNHL, and to provide the theoretical evidence for the diagnosis of this disease.

METHODSBlood samples were obtained from 2 pedigrees and 14 sporadic patients with SNHL. DNA was extracted from the isolated leukocytes. The mitochondrial DNA (mtDNA) fragments were amplified by PCR. The 1555(G), 3243(G) and 7445(G) mutation was detected by Alw 26 I, Apa I and Xba I restriction endonuclease digestion respectively. The sequence of 12S rRNA, tRNA(Leu(UUR)) and tRNA(Ser(UCN)) was examined.

RESULTSRestriction endonuclease digestion analysis showed that 12 individuals from 2 pedigrees carried homoplasmic 7445(G) mutation, which was of maternal inheritance. Six individuals from 2 pedigrees and 14 sporadic patients did not have 7445(G) mutation. All individuals did not have 1555(G) and 3243(G) mutation. The sequence analysis further showed that none of them carried homoplasmic 1555(G) and 3243(G) mutation, 12 individuals had (nt)7445 A--> G substitution in tRNA(Ser(UCN)) gene.

CONCLUSIONThe incidence of 7445(G) mutation in such pedigrees is higher than that in sporadic patients. Screening for mtDNA 7445(G) mutation combined with 1555(G) examination is of much value to clinical use.

DNA Mutational Analysis ; methods ; DNA, Mitochondrial ; genetics ; Female ; Hearing Loss, Sensorineural ; genetics ; Humans ; Male ; Pedigree ; Point Mutation ; RNA, Transfer, Ser ; genetics

Mitochondrial tRNAgene mutation is closely related to acoustic nerve deafness. Some mutations can affect the structure and transcriptional processing of tRNA, for instance m.7444G>A mutation in tRNAprecursor 3' side, m.7472 insC as well as m.7511T>C mutations in the stem and ring of tRNA, may influence tRNAstability, thus affect the synthesis of mitochondrial peptides, reduce the production of ATP and cause deafness. This article focuses on mitochondrial tRNAgene mutations as well as the mechanism underlying hearing loss.
Amino Acid Sequence ; Base Sequence ; Genetic Predisposition to Disease ; genetics ; Hearing Loss ; genetics ; Humans ; Mitochondrial Proteins ; biosynthesis ; genetics ; Mutation ; Nucleic Acid Conformation ; RNA ; chemistry ; genetics ; RNA, Transfer, Ser ; chemistry ; genetics

OBJECTIVETo identify the possible mutation at possible sites in different mitochondrial genes that leads to hearing loss in a large Chinese pedigree.

METHODSBlood samples from a Hunan pedigree were obtained with informed consent. Genomic DNA was extracted from peripheral blood leukocytes using kit. The target fragments were amplified and detected by polymerase chain reaction (PCR) and directly sequencing respectively.

RESULTSThe result of direct sequencing revealed the A1555G mutation in 12S rRNA gene was inherited in this pedigree and no one has A7445G mutation or other mutations in its neighborhood region.

CONCLUSIONSequence analysis confirmed that the pedigree carries the A1555G mutation. With some members ever exposure of aminoglycoside antibiotics, mutation of A1555G may play a pivotal role in the pathogenesis of hearing loss in the large pedigree.

Base Sequence ; China ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Family Health ; Female ; Hearing Loss ; genetics ; Humans ; Male ; Marriage ; Pedigree ; Polymerase Chain Reaction ; RNA, Ribosomal ; genetics ; RNA, Transfer, Ser ; genetics