Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T-->A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. -->

Jazyk:	English
ISSN:	0002-9297
Přístupová URL adresa:	https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::ff5f15cd9b5a127ca4bc64c82e30057d https://europepmc.org/articles/PMC1914692/
Rights:	OPEN
Přírůstkové číslo:	edsair.pmid.dedup....ff5f15cd9b5a127ca4bc64c82e30057d
Autor:	Vries, D. D., Went, L. N., Bruyn, G. W., Scholte, H. R., Robert Hofstra, Bolhuis, P. A., Oost, B. A.
Jazyk:	angličtina
Rok vydání:	1996
Předmět:	Adult Male DNA Mutational Analysis Molecular Sequence Data COMPLETE NUCLEOTIDE-SEQUENCE ORGANIZATION Citrate (si)-Synthase RED FIBERS MERRF DNA Mitochondrial Electron Transport DNA HETEROPLASMY Gene Frequency Optic Atrophies Hereditary NAD(P)H Dehydrogenase (Quinone) Humans Point Mutation SEGREGATION Amino Acid Sequence Muscle Skeletal NADH Dehydrogenase ITALIAN FAMILIES Middle Aged eye diseases Pedigree GENOME Dystonia NEURORETINOPATHY Phenotype MTDNA MUTATION CELLS Female Oxidoreductases Research Article
Zdroj:	American Journal of Human Genetics, 58(4), 703-711. CELL PRESS Scopus-Elsevier
ISSN:	0002-9297
Popis:	A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A-->G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T-->A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy.
Databáze:	OpenAIRE
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