Phenotypic variability of mitochondrial disease caused by a nuclear mutation in complex II.
We report a patient with relatively mild Leigh syndrome and mitochondrial respiratory chain complex II deficiency caused by a homozygous G555E mutation in the nuclear encoded flavoprotein subunit of succinate dehydrogenase. This mutation has previously been reported in a lethal-infantile presentation of complex II deficiency. Such marked phenotypic heterogeneity, although typical of heteroplasmic mutations in the mitochondrial genome, is unusual for nuclear mutations. Comparable activities and stability of mitochondrial respiratory chain enzymes were demonstrated in both patients, so other reasons for the phenotypic variability are considered.
Pagnamenta
Alistair T
AT
Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, UK.
Hargreaves
Iain P
IP
Duncan
Andrew J
AJ
Taanman
Jan-Willem
JW
Heales
Simon J
SJ
Land
John M
JM
Bitner-Glindzicz
Maria
M
Leonard
James V
JV
Rahman
Shamima
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D042963:Electron Transport Complex II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007033:Hypothalamus, Middle / Q000000981:diagnostic imaging; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D014451:Ubiquinone / Q000378:metabolism
D018076:DNA, Complementary; D021122:Protein Subunits; D014451:Ubiquinone; D042963:Electron Transport Complex II