title: Segregation pattern and biochemical effect of the G3460A mtDNA mutation in 27 members of LHON family.
abstract: Inheritance and expression of mitochondrial DNA (mtDNA) mutations are crucial for the pathogenesis of Leber hereditary optic neuropathy (LHON). We have investigated the segregation and functional consequences of G3460A mtDNA mutation in 27 members of a three-generation family with LHON syndrome. Specific activity of respiratory chain complex I in platelets was reduced in average to 56%, but no direct correlation between the mutation load and its biochemical expression was found. Heteroplasmy in blood, platelets and hair follicles varied from 7% to 100%. Segregation pattern exhibited tissue specificity and influence of different nuclear backgrounds in four branches of the pedigree. Longitudinal analysis revealed a significant (p=0.02) decrease in blood mutation load. Although enzyme assay showed reduction of complex I activity, our results give additional support to the hypothesis that expression of LHON mutation depends on complex nuclear-mitochondrial interaction.
authors.affiliation: Institute of Physiology and Center for Integrated Genomics, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 142 20, Czech Republic.
authors.forename: Vilma
authors.initials: V
authors.lastname: Kaplanová
authors.forename: Jirí
authors.initials: J
authors.lastname: Zeman
authors.forename: Hana
authors.initials: H
authors.lastname: Hansíková
authors.forename: Leona
authors.initials: L
authors.lastname: Cerná
authors.forename: Hana
authors.initials: H
authors.lastname: Houst'ková
authors.forename: Nadezda
authors.initials: N
authors.lastname: Misovicová
authors.forename: Josef
authors.initials: J
authors.lastname: Houstek
mesh_terms: D000409:Alanine / Q000235:genetics; D000704:Analysis of Variance; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D005192:Family Health; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009243:NAD / Q000097:blood; D029242:Optic Atrophy, Hereditary, Leber / Q000097:blood / Q000235:genetics*; D010088:Oxidoreductases / Q000097:blood; D010375:Pedigree; D017354:Point Mutation; D012402:Rotenone
chemical_list: D004272:DNA, Mitochondrial; D012402:Rotenone; D009243:NAD; D010088:Oxidoreductases; D000409:Alanine; D005998:Glycine