Mitochondrial variant G4132A is associated with familial non-arteritic anterior ischemic optic neuropathy in one large pedigree.
OBJECTIVE
To identify the genetic factors associated with familial non-arteritic anterior ischemic optic neuropathy (NA-AION) in a large pedigree.


METHODS
Eleven family members of a single pedigree, including six affected with NA-AION, underwent detailed clinical examinations. The mitochondrial DNA of the proband was sequenced in its entirety in search of disease-causing mutations associated with NA-AION in the pedigree. A control panel comprising 1488 patients suspected of having Leber hereditary optic neuropathy (LHON) and 97 general-population control subjects was screened for the mitochondrial sequence variant identified in the family.


RESULTS
Affected family members were all male and exhibited classic features of NA-AION. Their mean age was 50.2 +/- 5.0 years. A total of 23 sequence variations were detected in the mitochondrial genome of the proband, including one novel sequence variation (G4132A, Ala276Thr) in the NADH dehydrogenase subunit 1 gene (ND1). The G4132A mitochondrial variant was detected in six members of a single pedigree with NA-AION. The G4132A variation was not observed in any of the 1585 subjects in the control panel. Moreover, this variant was not identified in over 2469 ethnically diverse individuals previously evaluated through the Human Mitochondrial Genome Database. None of the three major mutations associated with LHON (G3460A, G11778A, T14484C) were identified in the family.


CONCLUSIONS
The G4132A mitochondrial variation is associated with familial NA-AION in our pedigree.
Fingert
John H
JH
Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Grassi
Michael A
MA
Janutka
Josesph C
JC
East
Jade S
JS
Howard
James G
JG
Sheffield
Val C
VC
Jacobson
Dan M
DM
Hayreh
Sohan S
SS
Stone
Edwin M
EM
D019943:Amino Acid Substitution; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics*; D018917:Optic Neuropathy, Ischemic / Q000235:genetics*; D010375:Pedigree; D010446:Peptide Fragments / Q000737:chemistry; D018807:Polymorphism, Single-Stranded Conformational
D004272:DNA, Mitochondrial; D010446:Peptide Fragments; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human