title: Identification of a deletion in the NDUFS4 gene using array-comparative genomic hybridization in a patient with suspected mitochondrial respiratory disease.
abstract: We evaluated a patient, born after a normal 38-week pregnancy, with psychomotor retardation, poor coordination of ocular movements, recurrent vomiting and severe lactic acidosis. The patient was admitted to hospital at 2 months of age because of a mitochondrial-like syndrome and died at the age of 4.5 months. Array-comparative genomic hybridization (a-CGH) analysis revealed a homozygous deletion in 5q11.2 involving NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18 kDa (NADH-coenzyme Q reductase; NDUFS4). Both parents were heterozygous for the mutation. The array revealed a deletion of ~32kb that includes exon 2 of NDUFS4 subsequently confirmed by real time-PCR and multiplex PCR. NDUFS4 was previously correlated to Leigh syndrome since mutations in this gene block the assembly of complex I. This result demonstrates the relevance of a-CGH screening in patients affected by metabolic disorders of unknown etiology.
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy; CEINGE-Biotecnologie Avanzate, Naples, Italy. Electronic address: lombardo@ceinge.unina.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lombardo
authors.affiliation: CEINGE-Biotecnologie Avanzate, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ceglia
authors.affiliation: CEINGE-Biotecnologie Avanzate, Naples, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Tarsitano
authors.affiliation: U.O.C. di Pediatria, Presidio Ospedaliero dell'Immacolata, Sapri, Italy.
authors.forename: Ippolito
authors.initials: I
authors.lastname: Pierucci
authors.affiliation: CEINGE-Biotecnologie Avanzate, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy; CEINGE-Biotecnologie Avanzate, Naples, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Pastore
mesh_terms: D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D055028:Comparative Genomic Hybridization; D042967:Electron Transport Complex I; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D023061:Gene Order; D006720:Homozygote; D006801:Humans; D007223:Infant; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics*; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human
keywords: 5q11.2 deletion; ATP Synthase 6; ATPase6; CNVs; Leigh syndrome; Metabolic disorders; NADH dehydrogenase (ubiquinone) Fe–S protein 4, 18kDa (NADH-coenzyme Q reductase); NDUFS4; PCR; SURF1; a-CGH; array-comparative genomic hybridization; copy number variants; polymerase chain reaction; surfeit 1