Summary
Pearson syndrome is a multisystem mitochondrial disorder of infancy that is associated with deletions in the mitochondrial DNA (mtDNA) genome. We report a study on a male infant with Pearson syndrome. Assessment of oxidative phosphorylation activity indicated combined respiratory-chain defects in muscle, liver and fibroblasts; in particular, activity of complex I was reduced. Analysis of the patient's mtDNA identified a novel heteroplasmic 2.461 kb deletion, present at levels greater than 50% of the total mtDNA in the tissues examined. The deletion spanned nucleotides 10368 to 12828 and was flanked by a 3 bp GCC direct repeat sequence. Gene sequences affected are subunits 3, 4, 4L and 5 of complex I, and tRNAs for arginine, histidine, serine and leucine. Our findings correlate with the multiorgan involvement observed in Pearson syndrome.
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References
Anderson S, Bankier AT, Barrell BG et al (1981) Sequence and organization of the human mitochondrial genome.Nature 290: 457–465.
Bindoff LA, Desnuelle C, Birchmachin MA et al (1991) Multiple defects of the mitochondrial respiratory chain in a mitochondrial encephalopathy (MERRF) — a clinical, biochemical and molecular study.J Neurol Sci 102: 17–24.
Chretien D, Bourgeron T, Rotig A, Munnich A, Rustin P (1990) The measurement of the rotenone-sensitive NADH cytochromec reductase activity in mitochondria isolated from minute amount of human skeletal muscle.Biochem Biophys Res Commun 173: 26–33.
Cormier V, Rotig A, Quartino AR et al (1990) Widespread multi-tissue deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome.J Pediatr 117: 599–602.
Majander A, Suomalainen A, Vettenranta K et al (1991) Congenital hypoplastic anemia, diabetes, and severe renal tubular dysfunction associated with a mitochondrial DNA deletion.Pediatr Res 30: 327–330.
McShane MA, Hammans SR, Sweeney M et al (1991) Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA.Am J Hum Genet 48: 39–42.
Nelson I, Bonne G, Degoul F, Marsac C, Ponsot G, Lestienne P (1992) Kearns-Sayre syndrome with sideroblastic anemia: molecular investigations.Neuropediatrics 23: 199–205.
Pearson HA, Lobel JS, Kocoshis SA et al (1979) A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction.J Pediatr 95: 976–984.
Rotig A, Colonna M, Bonnefont JP et al (1989) Mitochondrial DNA deletion in Pearson's marrow/pancreas syndrome.Lancet 1: 902–903.
Rotig A, Cormier V, Blanche S et al (1990) Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy.J Clin Invest 86: 1601–1608.
Rotig A, Cormier V, Koll F et al (1991) Site-specific deletions of the mitochondrial genome in the pearson marrow pancreas syndrome.Genomics 10: 502–504.
Saiki RK, Gelfand DH, Stoffel S et al (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.Science 239: 487–491.
Zheng X, Shoffner JM, Voljavec AS, Wallace DC (1990) Evaluation of procedures for assaying oxidative phosphorylation enzyme activities in mitochondrial myopathy muscle biopsies.Biochim Biophys Acta 1019: 1–10.
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Kapsa, R., Thompson, G.N., Thorburn, D.R. et al. A novel mtDNA deletion in an infant with Pearson syndrome. J Inherit Metab Dis 17, 521–526 (1994). https://doi.org/10.1007/BF00711584
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DOI: https://doi.org/10.1007/BF00711584