A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population. Issue 3 (27th September 2016)

• Record Type: Journal Article
• Authors: Lamont, Ryan E.; Beaulieu, Chandree L.; Bernier, Francois P.; Sparkes, Rebecca; Innes, A. Micheil; Jackel‐Cram, Candice; Ober, Carole; Parboosingh, Jillian S.; Lemire, Edmond G.
• Is Part Of: American journal of medical genetics. Volume 173:Issue 3(2017)
• Page Start: 596
• Page End: 600
• Publication Date: 2016-09-27
• Subjects: electron transport complex I -- NDUFS4 -- genes, recessive -- genetic diseases, inborn -- Leigh disease -- Hutterite -- founder effect -- subacute necrotizing encephalomyelopathy -- mitochondrial diseases; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37983
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : 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.