Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
2008

Genetic Linkage of Frontotemporal Lobar Degeneration and Motor Neuron Disease

Sample size: 16 publication Evidence: high

Author Information

Author(s): Luty Agnes A, Kwok John B, Thompson Elizabeth M, Blumbergs Peter, Brooks William S, Loy Clement T, Dobson-Stone Carol, Panegyres Peter K, Hecker Jane, Nicholson Garth A, Halliday Glenda M, Schofield Peter R

Primary Institution: Prince of Wales Medical Research Institute, Sydney, NSW, Australia

Hypothesis

The study aims to identify the genetic locus associated with frontotemporal lobar degeneration and motor neuron disease in a multi-generational Australian family.

Conclusion

The study suggests that the chromosome 9 locus may be more telomeric than previously predicted, and highlights the potential misclassification of late-onset Alzheimer's disease patients in linked pedigrees.

Supporting Evidence

  • Neuropathological examination revealed TDP-43 protein deposition in affected individuals.
  • A family member with clinical Alzheimer's disease shared the disease haplotype.
  • The study achieved a maximal two-point LOD score of 3.24, indicating significant linkage.

Takeaway

This study looked at a family with a type of brain disease and found a specific area on chromosome 9 that might be important for understanding their condition.

Methodology

The study involved clinical review, neuropathological analysis, genome-wide scans, and DNA sequencing of candidate genes.

Potential Biases

Potential bias due to reliance on a single pedigree for linkage analysis.

Limitations

The study's findings may not be generalizable due to the focus on a single family.

Participant Demographics

The family is of Anglo-Celtic origin, with affected members spanning three generations.

Statistical Information

P-Value

3.24

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1471-2377-8-32

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