title: A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency.
abstract: We report a 16-month-old boy with psychomotor regression, muscle hypotonia, peripheral neuropathy, and lactic acidosis. Brain magnetic resonance imaging showed a bilateral abnormal signal in the substantia nigra and in the subthalamic nucleus, suggestive of Leigh disease. Histochemical analysis of skeletal muscle showed decreased cytochrome-c oxidase activity. Biochemical analysis of respiratory chain enzymes in muscle homogenate and in cultured fibroblasts showed isolated cytochrome-c oxidase deficiency. Western blot analysis in fibroblasts showed the absence of Surf1 protein. Genetic analysis of the SURF1 gene revealed that the patient was compound heterozygous for a previously reported mutation at the splice-junction site of intron 3 (240 + 1G > T), and for a novel 4-bp deletion in exon 6 (531_534delAAAT). Our data further enlarge the spectrum of mutations in SURF1 gene in patients with Leigh disease and cytochrome-c oxidase deficiency, contributing to better characterization of the clinical and neuroradiologic features of this group of patients for genotype-phenotype correlations.
authors.affiliation: Neuromuscular Diseases Unit, Department of Pediatrics, University of Genova, Istituto Giannina Gaslini, Italy. claudiobruno@ospedale-gaslini.ge.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.forename: Claudia
authors.initials: C
authors.lastname: Biedi
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Laura Doria
authors.initials: LD
authors.lastname: Lamba
authors.forename: Massimo
authors.initials: M
authors.lastname: Bado
authors.forename: Marilena
authors.initials: M
authors.lastname: Greco
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
mesh_terms: D001706:Biopsy; D015139:Blotting, Southern; D001921:Brain / Q000473:pathology; D030401:Cytochrome-c Oxidase Deficiency / Q000150:complications* / Q000201:enzymology; D004252:DNA Mutational Analysis; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000150:complications* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D017354:Point Mutation / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C094364:SURF4 protein, human