SDHA mutation with dominant transmission results in complex II deficiency with ocular, cardiac, and neurologic involvement.
Isolated defects of the mitochondrial respiratory complex II (succinate dehydrogenase, SDH) are rare, accounting for approximately 2% of all respiratory chain deficiency diagnoses. Here, we report clinical and molecular investigations of three family members with a heterozygous mutation in the large flavoprotein subunit SDHA previously described to cause complex II deficiency. The index patient presented with bilateral optic atrophy and ocular movement disorder, a progressive polyneuropathy, psychiatric involvement, and cardiomyopathy. Two of his children presented with cardiomyopathy and methylglutaconic aciduria in early childhood. The daughter deceased at the age of 7 months due to cardiac insufficiency. The 30-year old son presents with cardiomyopathy and developed bilateral optic atrophy in adulthood. Of the four nuclear encoded proteins composing complex II (SDHA, SDHB, SDHC, SDHD) and currently known assembly factors SDHAF1 and SDHAF2 mainly recessively inherited mutations have been described in SDHA, SDHB, SDHD, and SDHAF1 to be causative for mitochondrial disease phenotypes. This is the second report presenting autosomal dominant inheritance of a SDHA mutation.© 2016 Wiley Periodicals, Inc.
Division of Human Genetics, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Carolina
C
Courage
Division of Inherited Metabolic Diseases, Institute of Clinical Chemistry, Inselspital, Bern, Switzerland.|Biomedicum Helsinki, Research Program for Molecular Neurology, University of Helsinki, Helsinki, Finland.
Christopher B
CB
Jackson
Division of Inherited Metabolic Diseases, Institute of Clinical Chemistry, Inselspital, Bern, Switzerland.
Dagmar
D
Hahn
Biomedicum Helsinki, Research Program for Molecular Neurology, University of Helsinki, Helsinki, Finland.
Liliya
L
Euro
Division of Inherited Metabolic Diseases, Institute of Clinical Chemistry, Inselspital, Bern, Switzerland.
Jean-Marc
JM
Nuoffer
Division of Human Genetics, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Sabina
S
Gallati
Division of Human Genetics, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
André
A
Schaller
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000483:Alleles; D019943:Amino Acid Substitution; D015415:Biomarkers; D003062:Codon; D004252:DNA Mutational Analysis; D042963:Electron Transport Complex II / Q000172:deficiency*; D017809:Fatal Outcome; D005260:Female; D050259:Genes, Mitochondrial; D005838:Genotype; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D013385:Succinate Dehydrogenase / Q000737:chemistry / Q000235:genetics*
D015415:Biomarkers; D003062:Codon; C491545:SDHD protein, human; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase
SDHA; cardiomyopathy; complex II deficiency; mitochondrial disorder; optic atrophy