[The analysis of Leber's hereditary optic neuropathy associated with mitochondrial tRNAAla C5601T mutation in seven Han Chinese families].
We reported here the clinical, genetic, and molecular characterization of Leber's hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families.
Giuseppe Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou, China.
Hui-Hui
HH
Zhou
Xian-Ning
XN
Dai
Bei
B
Lin
Hui
H
Mi
Xiao-Ling
XL
Liu
Fu-Xin
FX
Zhao
Juan-Juan
JJ
Zhang
Xiang-Tian
XT
Zhou
Yan-Hong
YH
Sun
Qi-Ping
QP
Wei
Jia
J
Qu
Min-Xin
MX
Guan
D000293:Adolescent; D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002417:Cattle; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics*; D017421:Sequence Analysis; D014982:Xenopus laevis; D055815:Young Adult
D004272:DNA, Mitochondrial; D012343:RNA, Transfer