title: The NDUFB11 gene is not a modifier in Leber hereditary optic neuropathy.
abstract: Over 95% of Leber hereditary optic neuropathy (LHON) cases are due to mutations in mitochondrial DNA-encoded subunits of NADH:ubiquinone oxidoreductase (E.C.1.6.5.3., complex I). A recessive X-linked susceptibility gene that acts synergistically with the primary mtDNA mutation to produce visual loss is suggested by the high male-to-female ratio among LHON patients. The ESSS protein is a recently isolated subunit of bovine heart mitochondrial complex I. We revisited the genomic sequence of NDUFB11, the human homolog mapping to chromosome Xp11.23, and identified two mRNA isoforms showing different expression profiles in human tissues. Cultured skin fibroblasts from four LHON patients showed a pattern of expression similar to normal controls. Moreover, NDUFB11 did not seem to influence risk and age at onset of visual loss in a total of 65 individuals from 35 Italian LHON families. Also, the gene was not affected in 11 children with a severe encephalopathy associated with decreased complex I activity in skeletal muscle.
authors.affiliation: Department of Medical Biochemistry, Medical Biology and Medical Physics, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy. v.petruzzella@biochem.uniba.it
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Alessandra
authors.initials: A
authors.lastname: Torraco
authors.forename: Fabiana
authors.initials: F
authors.lastname: Fattori
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Elena
authors.initials: E
authors.lastname: Cardaioli
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000235:genetics; D012016:Reference Values
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; C518653:NDUFB11 protein, human; D021122:Protein Subunits; D004247:DNA; D042967:Electron Transport Complex I