title: A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family.
abstract: Leber's hereditary optic neuropathy (LHON) is a frequent cause of inherited blindness. A routine screening for common mtDNA mutations constitutes an important first in its diagnosis. However, a substantial number of LHON patients do not harbor known variants, both pointing to the genetic heterogeneity of LHON and bringing into question its genetic diagnosis. We report a familial case that exhibited typical features of LHON but lacked any of the common mutations. Genetic analysis revealed a novel pathogenic defect in the ND6 gene at 14279A that was not detected in any haplogroup-matched controls screened for it, nor has it been previously reported. This mutation causes a substantial conformational change in the secondary structure of the polypeptide matrix coil and may explain the LHON expression. Thus, it expands the spectrum of deleterious changes affecting ND6-encoding subunit and further highlights the functional significance of this gene, providing additional clues to the disease pathogenesis.
authors.affiliation: Department of Anthropology, University of Pennsylvania, Philadelphia, PA, USA. siz001@jefferson.edu
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Zhadanov
authors.forename: Vasily V
authors.initials: VV
authors.lastname: Atamanov
authors.forename: Nikolay I
authors.initials: NI
authors.lastname: Zhadanov
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Oleinikov
authors.forename: Ludmila P
authors.initials: LP
authors.lastname: Osipova
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Schurr
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013045:Species Specificity; D044465:White People
chemical_list: D004272:DNA, Mitochondrial; D007930:Leucine