Sequence analysis of the mitochondrial genome from a large family with maternally inherited nonsyndromic deafness.
OBJECTIVE
To ascertain whether other variations coexist with 1555(A--> G) mutation in the mitochondrial DNA and may aggravate the severity of hearing loss or increase the penetrance of 1555(A--> G) mutation in a large family with maternally inherited nonsyndromic deafness in Huaiyin, Jiangsu province.


METHODS
PCR-restriction fragment length polymorphism (PCR-RFLP) was used to screen both the nt1555 and the nt7445 of the mitochondrial DNA from 27 maternal members in the core family; and then the mitochondrial genomes from two maternal members, and the 12S rRNA genes MTRNR1 and tRNA-Ser(UCN) gene MTTS1 from the others, were amplified by PCR-RFLP and were sequenced.


RESULTS
1555(A--> G) mutation in the mitochondrial DNA was reverified to be one of the major factors which cause maternally inherited nonsyndromic deafness and the cosegregation of 955-960(insC) and 1555(A--> G) was present in this family. Moreover, 7449 (insG), a novel homoplasmic mutation in the tRNA-Ser(UCN) gene, was found to co-exist with 1555(A--> G) mutation in two maternal members.


CONCLUSIONS
The cosegregation of 955-960(insC) and 1555(A--> G) implies that 955-960(insC) may synergistically cause hearing loss in the presence of an 1555(A--> G) mutation, serving as an aggravating factor to enhance the sensitivity to aminoglycosides, and may sometimes increase the penetrance of 1555(A--> G) mutation.
Zhang
Hai-jun
HJ
Genetics Research Center, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009 PR China.
Xu
Chun-hong
CH
Zhan
Yi-ju
YJ
Zhao
Su-ying
SY
Shan
Yun-feng
YF
Geng
Xue-xia
XX
Shan
Xiang-nian
XN
D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D054629:Genome, Mitochondrial / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
D004272:DNA, Mitochondrial