Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome
| ISSN: | 0340-6717 |
|---|---|
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa061d7e4372000f4ac0df03494e1fd5 https://pubmed.ncbi.nlm.nih.gov/12616398 |
| Rights: | CLOSED |
| Přírůstkové číslo: | edsair.doi.dedup.....aa061d7e4372000f4ac0df03494e1fd5 |
| Autor: | Paule Bénit, Yves Dumez, Sophie Lebon, Pierre Rustin, Noman Kadhom, Alice Goldenberg, Julie Steffann, Agnès Rötig, Marc Dommergues, Pascale de Lonlay, Dominique Chretien, Arnold Munnich |
| Rok vydání: | 2002 |
| Předmět: |
Genetics
Male Nuclear gene Electron Transport Complex I Mitochondrial Diseases Genetic heterogeneity Nonsense mutation NDUFV1 Locus (genetics) NADH Dehydrogenase Biology Pedigree Liver Codon Nonsense Microsatellite Humans Female NADH NADPH Oxidoreductases Leigh Disease Muscle Skeletal Gene Genotyping Genetics (clinical) Microsatellite Repeats |
| Zdroj: | Human genetics. 112(5-6) |
| ISSN: | 0340-6717 |
| Popis: | Complex I deficiency, the most common cause of mitochondrial disorders, accounts for a variety of clinical symptoms and its genetic heterogeneity makes identification of the disease genes particularly tedious. Indeed, most of the 43 complex I subunits are encoded by nuclear genes, only seven of them being mitochondrially encoded. In order to offer urgent prenatal diagnosis, we have studied an inbred/multiplex family with complex I deficiency by using microsatellite DNA markers flanking the putative disease loci. Microsatellite DNA markers have allowed us to exclude the NDUFS7, NDUFS8, NDUFV1 and NDUFS1 genes and to find homozygosity at the NDUFS4 locus. Direct sequencing has led to identification of a homozygous splice acceptor site mutation in intron 1 of the NDUFS4 gene (IVS1nt -1, G-->A); this was not found in chorion villi of the ongoing pregnancy. We suggest that genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families helps to identify the disease-causing mutation. More generally, we suggest giving consideration to a more systematic microsatellite analysis of putative disease loci for identification of disease genes in inbred/multiplex families affected with genetically heterogeneous conditions. |
| Databáze: | OpenAIRE |
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