Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations.
Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency. We describe four children with novel SURF1 mutations and unusual features: three had prominent renal symptoms and one had ragged red fibers in the muscle biopsy. We identified five pathogenic mutations in SURF1: two mutations were novel, an in-frame nonsense mutation (834G-->A) and an out-of-frame duplication (820-824dupTACAT). Although renal manifestations have not been described in association with SURF1 mutations, they can be part of the clinical presentation. Likewise, mitochondrial proliferation in muscle (with ragged red fibers) is most unusual in Leigh disease but might be part of an emerging phenotype.
Tay
Stacey K H
SK
Department of Neurology, Columbia University, New York, NY, USA.
Sacconi
Sabrina
S
Akman
H Ohran
HO
Morales
Judith F
JF
Morales
Augusto
A
De Vivo
Darryl C
DC
Shanske
Sara
S
Bonilla
Eduardo
E
DiMauro
Salvatore
S
D030401:Cytochrome-c Oxidase Deficiency / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000209:etiology; D007888:Leigh Disease / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C092928:Surf-1 protein