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.
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Abbreviations
- mtDNA:
-
mitochondrial DNA
- LS:
-
Leigh syndrome
- MRI:
-
magnetic resonance imaging
- np:
-
nucleotide position
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Acknowledgements
We thank the “Associazione Amici del Centro Dino Ferrari.” The Telethon “Bank of DNA, Nerve and Muscle Tissues” (no. GTF02008) was the source of the skeletal muscle samples used in this study. The Eurobiobank project QLTR-2001-02769 and R.F.2002 “Criobanca automatizzata di materiale biologico” are gratefully acknowledged.
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This research received support by “Progetto MIUR-CNR Genomica Funzionale” (to G.P.C.) and by “Ricerca Finalizzata 2002,” Ministero della Salute, Italy (to G.P.C.).
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Crimi, M., Papadimitriou, A., Galbiati, S. et al. A New Mitochondrial DNA Mutation in ND3 Gene Causing Severe Leigh Syndrome with Early Lethality. Pediatr Res 55, 842–846 (2004). https://doi.org/10.1203/01.PDR.0000117844.73436.68
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DOI: https://doi.org/10.1203/01.PDR.0000117844.73436.68
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