Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease

Neurology. 2009 May 12;72(19):1669-76. doi: 10.1212/WNL.0b013e3181a55f1c.


Background: Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21.3-p13.3).

Methods: Ten French families with FTD-MND were tested for linkage to the 9p21.3-p13.3 region. We report extensive mutation screening in 9p-linked families and their clinical characteristics.

Results: We identified six new families with evidence for linkage to the chromosome 9p. Cumulative multipoint LOD score values were positive between markers D9S1121 and D9S301, reaching a peak of 8.0 at marker D9S248. Haplotype reconstruction defined the telomeric boundary at marker AFM218xg11, slightly narrowing the candidate interval. We found no disease-causing mutations by sequencing 29 candidate genes including IFT74 and no copy number variations in the 9p region. The mean age at onset was 57.9 +/- 10.3 years (range, 41-84), with wide heterogeneity within and among families suggesting age-dependant penetrance. The patients presented isolated FTD (32%), isolated MND (29%), or both disorders (39%). The general characteristics of the disease did not differ, except for an older age at onset and shorter disease duration in the 9p-linked compared to nonlinked families. TDP-43-positive neuronal cytoplasmic inclusions were found in cortex and spinal cord in 3 patients.

Conclusions: This study increases the number of 9p-linked families now reported and shows that this locus may have a major effect on frontotemporal dementia (FTD) and motor neuron disease (MND). Considering our results, the causative gene might be implicated in at least 60% of the families with FTD-MND disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9 / genetics*
  • DNA Mutational Analysis
  • Dementia / complications
  • Dementia / genetics*
  • Female
  • Genetic Linkage / genetics*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Motor Neuron Disease / complications
  • Motor Neuron Disease / genetics*
  • Mutation / genetics*
  • Pedigree
  • Penetrance
  • Young Adult


  • Genetic Markers