A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality.
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.
Crimi
Marco
M
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
Papadimitriou
Alexandros
A
Galbiati
Sara
S
Palamidou
Phani
P
Fortunato
Francesco
F
Bordoni
Andreina
A
Papandreou
Urania
U
Papadimitriou
Dimitra
D
Hadjigeorgiou
George M
GM
Drogari
Eurydiki
E
Bresolin
Nereo
N
Comi
Giacomo Pietro
GP
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
D004272:DNA, Mitochondrial; D011506:Proteins; D019344:Lactic Acid; D019289:Pyruvic Acid; D042967:Electron Transport Complex I; C114961:MT-ND3 protein, human