[Leber's hereditary optic neuropathy may be associated with the mitochondrial tRNAGlu A14693G mutation in three Chinese families].
We reported here the clinical, genetic and molecular characterization of three Han Chinese families with Leber's hereditary optic neuropathy. Ophthalmologic examinations revealed the variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of these families. Strikingly, these families exhibited extremely low penetrances of visual impairment. Sequence analysis of complete mitochondrial genomes in these pedigrees identified the known homoplasmic tRNAGlu A14693G mutation and distinct sets of polymorphism belonging to haplogroups Y1b, Y1 and Y1, respectively. The A14693G mutation occurs at the extremely conserved nucleotide (conventional position 54) of tRNAGlu. Thus, this mutation may alter structural formation and stabilization of functional tRNAs, thereby leading to a failure in tRNA metabolism and mitochondrial dysfunction involved in visual impairment. However, none of other variants showed the evolutionary conservation and functional significance. These observations suggested that the tRNAGlu A14693G mutation may be involved in the pathogenesis of optic neuropathy in these families.
Zhang
Yong-Mei
YM
Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China zhangyongmei0529@163.com
Ji
Yan-Chun
YC
Liu
Xiao-Ling
XL
Zhou
Xiang-Tian
XT
Zhao
Fu-Xin
FX
Sun
Yan-Hong
YH
Wei
Qi-Ping
QP
Zhang
Juan-Juan
JJ
Liu
Yan
Y
Qu
Jia
J
Guan
Min-Xin
MX
D000293:Adolescent; D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D012343:RNA, Transfer / Q000235:genetics*
D012343:RNA, Transfer