A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality

• Published in: Pediatric research Vol. 55; no. 5; pp. 842 - 846
• Main Authors: CRIMI, Marco, PAPADIMITRIOU, Alexandros, BRESOLIN, Nereo, COMI, Giacomo Pietro, GALBIATI, Sara, PALAMIDOU, Phani, FORTUNATO, Francesco, BORDONI, Andreina, PAPANDREOU, Urania, PAPADIMITRIOU, Dimitra, HADJIGEORGIOU, George M, DROGARI, Eurydiki
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.05.2004
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Brain - pathology; DNA, Mitochondrial - genetics; Electron Transport; Electron Transport Complex I - genetics; Family Health; Female; Fundamental and applied biological sciences. Psychology; General aspects; Genetics of eukaryotes. Biological and molecular evolution; Humans; Infant; Lactic Acid - blood; Lactic Acid - cerebrospinal fluid; Leigh Disease - genetics; Leigh Disease - mortality; Magnetic Resonance Imaging; Male; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Muscles - metabolism; Mutation; Polymorphism, Restriction Fragment Length; Proteins - genetics; Pyruvic Acid - blood; Pyruvic Acid - cerebrospinal fluid; Sequence Homology, Amino Acid; Pediatrics; Nervous system diseases; Leigh disease; Critically ill; Metabolic diseases; Mitochondrial DNA; Enzymopathy; Mitochondrial disorder; Cerebral disorder; Genetic disease; Gene; Central nervous system disease; Genetics; Early; Mutation; Severe
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/01.PDR.0000117844.73436.68

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.