A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population.
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.
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.
Ryan E
RE
Lamont
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.
Chandree L
CL
Beaulieu
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.
Francois P
FP
Bernier
Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Rebecca
R
Sparkes
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.
A Micheil
AM
Innes
Division of Medical Genetics, Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada.
Candice
C
Jackel-Cram
Department of Human Genetics, University of Chicago, Chicago, Illinois.
Carole
C
Ober
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.
Jillian S
JS
Parboosingh
Division of Medical Genetics, Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada.
Edmond G
EG
Lemire
D002170:Canada; D003241:Consanguinity; D004252:DNA Mutational Analysis; D042967:Electron Transport Complex I; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D014481:United States
D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human
Hutterite; Leigh disease; NDUFS4; electron transport complex I; founder effect; genes, recessive; genetic diseases, inborn; mitochondrial diseases; subacute necrotizing encephalomyelopathy