title: A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality.
abstract: We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patient's development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Laboratory examination showed increased lactate and pyruvate in both serum and cerebrospinal fluid. Brain magnetic resonance imaging revealed multiple necrotic lesions in the basal ganglia, brain stem, and thalamus. Muscle histopathology was unremarkable, whereas respiratory chain enzyme analysis revealed a severe complex I deficiency. The patient died after an acidotic coma at age 9 mo. Sequence analysis of the entire mtDNA disclosed a new T10158C mutation with variable tissue heteroplasm (muscle: 83%; blood: 48%). The mutation was undetectable in the blood of his unaffected mother. The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality.
authors.affiliation: Centro Dino Ferrari, Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centro di Eccellenza per le malattie Neuro-Degenerative, 20122 Milano, Italy. neurogene@policlinico.mi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Crimi
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: Sara
authors.initials: S
authors.lastname: Galbiati
authors.forename: Phani
authors.initials: P
authors.lastname: Palamidou
authors.forename: Francesco
authors.initials: F
authors.lastname: Fortunato
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Urania
authors.initials: U
authors.lastname: Papandreou
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.forename: George M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.forename: Eurydiki
authors.initials: E
authors.lastname: Drogari
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D019344:Lactic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D007888:Leigh Disease / Q000235:genetics* / Q000401:mortality*; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics*; D019289:Pyruvic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D017386:Sequence Homology, Amino Acid
chemical_list: D004272:DNA, Mitochondrial; D011506:Proteins; D019344:Lactic Acid; D019289:Pyruvic Acid; D042967:Electron Transport Complex I; C114961:MT-ND3 protein, human