[Leber's hereditary optic neuropathy and limbs abnormity claudication may be associated with the mitochondrial ND1 T3866C mutation].
Mutations in mitochondrial DNA have been associated with a wide spectrum of clinical abnormalities. We reported here the clinical, genetic and molecular characterization of a five-generation Han Chinese pedigree with Leber's Hereditary Optic Neuropathy (LHON) and limbs abnormity claudication. Of 27 matrilineal relatives, four exhibited only LHON, one suffered from only limbs abnormity claudication, and four had both LHON and limbs abnormity claudication. Sequence analysis of mitochondrial genome in this family identified the known T3866C mutation in ND1 gene and other 43 variants belonging to the Asian haplogroup D4a3. The T3866C (I187T) mutation resulted in the replacement of isoleucine at position 187 with theronine. The isoleucine at position 187 located at one of transmembrane domain in ND1 polypeptide. The isoleucine at position 187 was extremely conserved among 29 organisms, while other variants showed no evolutionarily conservation. Furthermore, the T3866C was absence in 135 Chinese control subjects. The T3866C mutation likely alters the complex I activity, which causes mitochondrial dysfunction associated with LHON and limbs abnormity claudication. Therefore, the T3866C mutation is likely associated with LHON and limbs abnormity claudication.
Liu
Yan
Y
Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China. liuyan6607@126.com
Zhuang
Shu-Liu
SL
Tong
Yi
Y
Qu
Jia
J
Zhou
Xiang-Tian
XT
Zhao
Fu-Xin
FX
Zhang
Juan-Juan
JJ
Zhang
Yong-Mei
YM
Zhang
Yu
Y
Guan
Min-Xin
MX
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005121:Extremities; D005260:Female; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation; D011487:Protein Conformation; D016415:Sequence Alignment; D055815:Young Adult
D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human