Clinical Trial: Identification of New FTLD Genes

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Identification of New Genes Causing Frontotemporal Lobar Degeneration by Whole Exome Sequencing and Characterization of the Associated Phenotypes

Brief Summary:

The major objective of the project is to map/identify new loci/genes, by a combination of whole exome sequencing and genome-wide linkage in autosomal dominant FTLD families excluded for known mutations.

Several secondary goals will be attained in the course of during the project:

For each novel gene identified in this project, we will determine the spectrum of mutations, evaluate their frequency and characterize the associated phenotypes. This will allow us to establish genotype-phenotype correlations in a large number of families, which will improve the nosology of these disorders and the diagnostic procedures;


Detailed Summary:

Background and justification of the research. In France, 6,000 to 8,000 patients are affected by frontotemporal lobar degeneration (FTLD). FTLD are degenerative dementias related to Alzheimer's disease, characterized by behavioural, language and cognitive disorders beginning in the sixth decade. The genetic forms of FTLD are frequent (30-50% of the patients), but the genes responsible for 30-40% of familial FTLD are still unknown. At present, no molecular diagnosis can be proposed for 30% of the FTLD families and patients, for which the responsible genes are still unknown. No presymptomatic testing can be proposed either to at-risk relatives in these families.

Objectives.

  1. The principal objective of this proposal is to identify one or several genes responsible for FTLD.

  2. The secondary objectives are to:

    • evaluate the relative frequency of identified genes;
    • describe the phenotypes associated with the mutations in these genes;
    • establish phenotype-genotype correlations in order to improve the diagnostic procedures and strategies;
    • develop new genetic diagnostic analyses in the near future.

Project The patients will be recruited in three hospitals (Paris Salpetriere, Limoges, Lille). These three centers are partners of a national clinico-genetic network of 20 french centers experts in FTLD/FTLD-ALS, coordinated by Dr. I Le Ber. The participants in this network have collaborated for the last 15 years, and have already recruited over 1,000 patients with FTLD. Sequencing
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: whole exome sequencing [ Time Frame: Day 1 ]

genes responsible for FTLD /Blood samples will be collected by a nurse, during a single consultation or hospitalization


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: February 9, 2015
Date Started: February 2015
Date Completion: February 2017
Last Updated: September 14, 2016
Last Verified: August 2016