title: Maternal segmental disomy in Leigh syndrome with cytochrome c oxidase deficiency caused by homozygous SURF1 mutation.
abstract: Cytochrome c oxidase deficiency (COX) is the most frequent cause of Leigh syndrome (LS), a mitochondrial subacute necrotizing encephalomyelopathy. Most of these LS (COX-) patients show mutations in SURF1 on chromosome 9 (9q34), which encodes a protein essential for the assembly of the COX complex. We describe a family whose first-born boy developed characteristic features of LS. Severe COX deficiency in muscle was caused by a novel homozygous nonsense mutation in SURF1. Segregation analysis of this mutation in the family was incompatible with autosomal recessive inheritance but consistent with a maternal disomy. Haplotype analysis of microsatellite markers confirmed isodisomy involving nearly the complete long arm of chromosome 9 (9q21-9tel). No additional physical abnormalities were present in the boy, suggesting that there are no imprinted genes on the long arm of chromosome 9 which are crucial for developmental processes. This case of segmental isodisomy illustrates that genotyping of parents is crucial for correct genetic counseling.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany. anne.van.riesen@web.de
authors.forename: A K J
authors.initials: AK
authors.lastname: van Riesen
authors.forename: H
authors.initials: H
authors.lastname: Antonicka
authors.forename: A
authors.initials: A
authors.lastname: Ohlenbusch
authors.forename: E A
authors.initials: EA
authors.lastname: Shoubridge
authors.forename: E K G
authors.initials: EK
authors.lastname: Wilichowski
mesh_terms: D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007888:Leigh Disease / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011506:Proteins / Q000235:genetics*; D024182:Uniparental Disomy / Q000175:diagnosis / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C092928:Surf-1 protein