Sequence analysis of the mitochondrial genome from a large family with maternally inherited nonsyndromic deafness.
- Author:
Hai-jun ZHANG
1
;
Chun-hong XU
;
Yi-ju ZHAN
;
Su-ying ZHAO
;
Yun-feng SHAN
;
Xue-xia GENG
;
Xiang-nian SHAN
Author Information
- Publication Type:Journal Article
- MeSH: DNA, Mitochondrial; chemistry; genetics; Deafness; genetics; Female; Genetic Predisposition to Disease; Genome, Mitochondrial; genetics; Humans; Male; Pedigree; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sequence Analysis, DNA
- From: Chinese Journal of Medical Genetics 2005;22(4):368-371
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo 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.
METHODSPCR-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.
RESULTS1555(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.
CONCLUSIONThe 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.