Homoplasmy of a mitochondrial 3697G>A mutation causes Leigh syndrome.
Herein we report on three siblings with Leigh syndrome (LS) harboring a homoplasmic m.3697G>A mutation (G131S) in the MT-ND1 gene. The siblings' phenotypically normal mother had the same, albeit heteroplasmic, mutation. Complex I deficiency (8% of average control values) was demonstrated in a biceps brachii muscle from one of the patients. Heteroplasmic m.3697G>A has been reported in patients with Leber's hereditary optic neuropathy, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes and Stüve-Wiedemann syndrome. Because all three patients in this series carried m.3697G>A in a homoplasmic manner and had LS, we suggest that homoplasmy of m.3697G>A may cause the LS phenotype.
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Yutaka
Y
Negishi
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Ayako
A
Hattori
National Center of Neurology and Psychiatry, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Kodaira, Japan.
Eri
E
Takeshita
National Center of Neurology and Psychiatry, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Kodaira, Japan.
Chika
C
Sakai
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Naoki
N
Ando
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Tetsuya
T
Ito
National Center of Neurology and Psychiatry, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Kodaira, Japan.
Yu-ichi
Y
Goto
Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Shinji
S
Saitoh
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005838:Genotype; D006801:Humans; D007888:Leigh Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics; D010641:Phenotype; D035781:Siblings
D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human