title: Sequence variations in the NDUFA1 gene encoding a subunit of complex I of the respiratory chain.
abstract: NDUFA1 is one of the 36 nuclear genes encoding subunits of the mitochondrial complex I involved in the respiratory chain. The human NDUFA1 has been cloned, completely sequenced and mapped to Xq24. In the present study, we searched for sequence variations in NDUFA1 as causative defects in complex I deficiency using genomic DNA of 152 patients with various clinical phenotypes. The patient sample consisted of 54 patients (46 male and 8 female) with Leber heriditary optic neuropathy (LHON) from 48 unrelated families from Germany and 98 patients (72 male and 26 female) with biochemically proven complex I deficiency including Leigh syndrome. Patient DNA was used to amplify all three exons, including the exon/intron boundaries and the promoter region of NDUFA1 for heteroduplex analysis and direct sequencing. In the 152 patients tested, no mutation was found that could be related to any of the disease phenotypes included. However, three single-nucleotide polymorphisms (SNPs) located in the promoter region (SNP G/C at nt -71 and SNP T/C at nt -189) and in intron 1 (SNP T/G nt 1454) were discovered. Allele frequencies of the SNPs were estimated in a German and Estonian control population and compared to complex I-deficient patients. There was no significant difference between the control population, the LHON patients, or the severely affected patients with complex I deficiency, excluding an association of the polymorphisms with the diseases. Our results suggest that mutations in NDUFA1 do not cause the gender difference observed in clinically severe and complex phenotypes with complex I deficiency.
authors: Institute of Human Genetics, Greifswald, Germany.
authors: I
authors: I
authors: Wittig
authors: P
authors: P
authors: Augstein
authors: G K
authors: GK
authors: Brown
authors: T
authors: T
authors: Fujii
authors: A
authors: A
authors: Rötig
authors: P
authors: P
authors: Rustin
authors: A
authors: A
authors: Munnich
authors: P
authors: P
authors: Seibel
authors: D
authors: D
authors: Thorburn
authors: B
authors: B
authors: Wissinger
authors: K
authors: K
authors: Tamboom
authors: A
authors: A
authors: Metspalu
authors: E
authors: E
authors: Lamantea
authors: M
authors: M
authors: Zeviani
authors: M S
authors: MS
authors: Wehnert
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis; D004579:Electron Transport; D042967:Electron Transport Complex I; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007888:Leigh Disease / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009245:NADH Dehydrogenase; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D009692:Nucleic Acid Heteroduplexes; D015418:Optic Atrophies, Hereditary / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; C492251:Ndufa1 protein, mammalian; D009692:Nucleic Acid Heteroduplexes; D009247:NADH, NADPH Oxidoreductases; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C118736:NDUFA1 protein, human