A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population.

Autor: Lamont RE; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada., Beaulieu CL; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada., Bernier FP; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada., Sparkes R; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Innes AM; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada., Jackel-Cram C; Division of Medical Genetics, Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada., Ober C; Department of Human Genetics, University of Chicago, Chicago, Illinois., Parboosingh JS; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada., Lemire EG; Division of Medical Genetics, Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2017 Mar; Vol. 173 (3), pp. 596-600. Date of Electronic Publication: 2016 Sep 27.
DOI: 10.1002/ajmg.a.37983
Abstrakt: Leigh disease is a progressive, infantile-onset, neurodegenerative disorder characterized by feeding difficulties, failure to thrive, hypotonia, seizures, and central respiratory compromise. Metabolic and neuroimaging investigations typically identify abnormalities consistent with a disorder of mitochondrial energy metabolism. Mutations in more than 35 genes affecting the mitochondrial respiratory chain encoded from both the nuclear and mitochondrial genomes have been associated with Leigh disease. The clinical presentations of five individuals of Hutterite descent with Leigh disease are described herein. An identity-by-descent mapping and candidate gene approach was used to identify a novel homozygous c.393dupA frameshift mutation in the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (NDUFS4) gene. The carrier frequency of this mutation was estimated in >1,300 Hutterite individuals to be 1 in 27. © 2017 Wiley Periodicals, Inc.
(© 2017 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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