The NDUFB11 gene is not a modifier in Leber hereditary optic neuropathy.
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.
Petruzzella
Vittoria
V
Department of Medical Biochemistry, Medical Biology and Medical Physics, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy. v.petruzzella@biochem.uniba.it
Tessa
Alessandra
A
Torraco
Alessandra
A
Fattori
Fabiana
F
Dotti
Maria Teresa
MT
Bruno
Claudio
C
Cardaioli
Elena
E
Papa
Sergio
S
Federico
Antonio
A
Santorelli
Filippo M
FM
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
D017931:DNA Primers; D004272:DNA, Mitochondrial; C518653:NDUFB11 protein, human; D021122:Protein Subunits; D004247:DNA; D042967:Electron Transport Complex I