Journal of Inherited Metabolic Disease

, Volume 31, Supplement 2, pp 461–467

A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family

  • S. L. Anderson
  • W. K. Chung
  • J. Frezzo
  • J. C. Papp
  • J. Ekstein
  • S. DiMauro
  • B. Y. Rubin
Short Report

DOI: 10.1007/s10545-008-1049-9

Cite this article as:
Anderson, S.L., Chung, W.K., Frezzo, J. et al. J Inherit Metab Dis (2008) 31(Suppl 2): 461. doi:10.1007/s10545-008-1049-9


Leigh syndrome is a neurodegenerative disorder of infancy or childhood generally due to mutations in nuclear or mitochondrial genes involved in mitochondrial energy metabolism. We performed linkage analysis in an Ashkenazi Jewish (AJ) family without consanguinity with three affected children. Linkage to microsatellite markers D5S1969 and D5S407 led to evaluation of the complex I gene NDUFS4, in which we identified a novel homozygous c.462delA mutation that disrupts the reading frame. The resulting protein lacks a cAMP-dependent protein kinase phosphorylation site required for activation of mitochondrial respiratory chain complex I. In a random sample of 5000 healthy AJ individuals, the carrier frequency of the NDUFS4 mutation c.462delA was 1 in 1000, suggesting that it should be considered in all AJ patients with Leigh syndrome.



Ashkenazi Jewish


BCS1-like protein


dihydrolipoamide dehydrogenase


magnetic resonance spectroscopy


NADH-ubiquinone oxidoreductase Fe-S proteins and flavoproteins


pyruvate dehydrogenase complex


reverse transcription polymerase chain reaction


succinate dehydrogenase complex, subunit A


surfeit 1

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • S. L. Anderson
    • 1
  • W. K. Chung
    • 2
  • J. Frezzo
    • 1
  • J. C. Papp
    • 3
  • J. Ekstein
    • 4
    • 5
  • S. DiMauro
    • 6
  • B. Y. Rubin
    • 1
  1. 1.Department of Biological SciencesFordham UniversityBronxUSA
  2. 2.Department of PediatricsColumbia University Medical CenterNew YorkUSA
  3. 3.Department of Human GeneticsUniversity of CaliforniaLos AngelesUSA
  4. 4.Dor YeshorimThe Committee for Prevention of Jewish Genetic DiseasesBrooklynUSA
  5. 5.Dor YeshorimThe Committee for Prevention of Jewish Genetic DiseasesJerusalemIsrael
  6. 6.Department of NeurologyColumbia University Medical CenterNew YorkUSA

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