Sequence variations in the NDUFA1 gene encoding a subunit of complex I of the respiratory chain

Sequence variations in the NDUFA1 gene encoding a subunit of complex I of the respiratory chain

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 d...

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Bibliographic Details
Published in:Journal of inherited metabolic disease Vol. 24; no. 1; pp. 15 - 27
Main Authors: Wittig, I., Augstein, P., Brown, G. K., Fujii, T., Rötig, A., Rustin, P., Munnich, A., Seibel, P., Thorburn, D., Wissinger, B., Tamboom, K., Metspalu, A., Lamantea, E., Zeviani, M., Wehnert, M. S.
Format: Journal Article
Language:English
Published: Dordrecht Kluwer Academic Publishers 01-02-2001
Springer
Blackwell Publishing Ltd
Subjects:
Alleles
Biological and medical sciences
DNA Mutational Analysis
Electron Transport
Electron Transport Complex I
Errors of metabolism
Female
Gene Frequency
Genetic Variation
Humans
Leigh Disease - genetics
Male
Medical sciences
Membrane Proteins - genetics
Metabolic diseases
Miscellaneous hereditary metabolic disorders
NADH Dehydrogenase
NADH, NADPH Oxidoreductases - deficiency
NADH, NADPH Oxidoreductases - genetics
Nucleic Acid Heteroduplexes
Optic Atrophies, Hereditary - genetics
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
Nucleotide sequence
Enzyme
Variations
Metabolic diseases
Subunit
Enzymopathy
Mitochondrial disorder
Genetic disease
Respiratory chain
Etiology
Oxidoreductases
Mutation
Molecular biology
NADH dehydrogenase (ubiquinone)
Polymorphism
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Summary: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.
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ISSN:0141-8955
1573-2665
DOI:10.1023/A:1005638218246