High prevalence of SURF1 c.845_846delCT mutation in Polish Leigh patients

Eur J Paediatr Neurol. 2009 Mar;13(2):146-53. doi: 10.1016/j.ejpn.2008.03.009. Epub 2008 Jun 26.

Abstract

Leigh syndrome is a neuropathological disorder with typical morphological changes in brain, appearing regardless of diverse molecular background. One of the most common enzymatic defects in Leigh patients is cytochrome c oxidase deficiency associated with recessive mutations in the SURF1 gene. To assess the SURF1 mutation profile among Polish patients we studied 41 affected children from 34 unrelated families by PCR-SSCP and sequencing. Four novel mutations, c.39delG, c.752-1G>C, c.800_801insT, c.821A>G, and five described pathogenic changes, c.311_312insAT312_321del10, c.688C>T, c.704T>C, c.756_757delCA, c.845_846delCT, were identified in 85.3% of analysed probands. One mutation, c.845_846delCT, was identified in 77.6% of SURF1 alleles. Up to now, it has been reported only in 9% of alleles in other parts of the world. The deletion was used as LS(SURF1-) marker in population studies. Eight heterozygous carriers of the mutation were found in a cohort of 2890 samples. The estimated c.845_846delCT allele frequency is 1:357 (0.28+/-0.2%), and the lowest predicted LS(SURF1-) frequency in Poland 1:126,736.births. Relatively high frequency of LS(SURF1-) in Poland with remarkable c.845_846delCT mutation dominance allows one to start the differential diagnosis of LS in each patient of Polish (and probably Slavonic) origin from the direct search for c.845_846delCT SURF1 mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochrome-c Oxidase Deficiency / epidemiology
  • Cytochrome-c Oxidase Deficiency / etiology
  • Cytochrome-c Oxidase Deficiency / genetics*
  • DNA Mutational Analysis / methods
  • Female
  • Gene Frequency
  • Heterozygote
  • Humans
  • Infant
  • Leigh Disease / diagnosis
  • Leigh Disease / epidemiology
  • Leigh Disease / etiology
  • Leigh Disease / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Mitochondrial Proteins / genetics*
  • Mutation*
  • Poland / epidemiology
  • Polymerase Chain Reaction
  • Prevalence
  • Sequence Deletion*

Substances

  • Membrane Proteins
  • Mitochondrial Proteins
  • Surf-1 protein