High frequency of the expanded C9ORF72 hexanucleotide repeat in familial and sporadic Greek ALS patients

Neurobiol Aging. 2012 Aug;33(8):1851.e1-5. doi: 10.1016/j.neurobiolaging.2012.02.021. Epub 2012 Mar 22.

Abstract

An intronic expansion of a hexanucleotide GGGGCC repeat in the C9ORF72 gene has recently been shown to be an important cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in familial and sporadic cases. The frequency has only been defined in a small number of populations where the highest sporadic rate was identified in Finland (21.1%) and the lowest in mainland Italy (4.1%). We examined the C9ORF72 expansion in a series of 146 Greek ALS cases, 10.95% (n = 16) of cases carried the pathological expansion defined as greater than 30 repeats. In the 10 familial ALS probands, 50% (n = 5) of them carried a pathologically large expansion. In the remaining 136 sporadic ALS cases, 11 were carriers (8.2%). None of the 228 Greek controls carried an expanded repeat. The phenotype of our cases was spinal (13/16) or bulbar (3/16) ALS, the familial cases were all spinal ALS and none of our cases had behavioral frontotemporal dementia. Expansions in the C9ORF72 gene therefore represent a common cause of ALS in Greece and this test will be diagnostically very important to implement in the Greek population. The frequency is higher than other populations with the exception of Finland and this may be due to Greece being a relatively isolated population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / congenital
  • Amyotrophic Lateral Sclerosis / epidemiology*
  • Amyotrophic Lateral Sclerosis / genetics*
  • C9orf72 Protein
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics
  • Greece / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence
  • Proteins / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Risk Factors

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • Genetic Markers
  • Proteins