Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00159198
Recruitment Status : Terminated (Completed)
First Posted : September 12, 2005
Last Update Posted : September 8, 2008
Information provided by:
Assistance Publique - Hôpitaux de Paris

September 7, 2005
September 12, 2005
September 8, 2008
September 2002
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Complete list of historical versions of study NCT00159198 on Archive Site
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Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD) is a rare clinical entity, in which both disorders are variably associated in the same patient or within the family. This adult-onset disorder, which is rapidly fatal, occurs in some families with autosomal dominant (AD) transmission and age-dependant penetrance. Two studies have provided evidence for linkage of this condition to chromosomes 15 (in a single family) and 9 (in five families). However, none of these loci have been yet confirmed. Through a national network of 10 centres with specialists for FTD and/or ALS, we have identified 35 probands with ALS-FTD, including 13 with a family history consistent with AD inheritance.

Mutations in the SOD1 and tau genes, respectively responsible for autosomal dominant forms of ALS and FTD, will be excluded by direct sequencing. We will then extend the pedigree of the 13 autosomal dominant families to all consenting first, second and eventually third degree relatives, using well defined criteria for FTD and ALS. The same strategy will be applied to newly identified families during the course of the project (at least, seven families with AD inheritance expected). Linkage studies will be performed in the 20 families using markers from the two candidate regions on chromosomes 9 and 15. Then, refinement of the candidate region will be obtained by analyzing the linked families with a high density of microsatellite markers. This should lead to the refinement of the candidate regions, allowing to search for mutations in candidate genes. Genes located within the critical regions will be prioritized for their analysis by sequencing, according to their expression in the nervous system and to their function.

Once the responsible gene(s) will be identified, it will then possible to define its spectrum of mutations and to establish genotype/phenotype correlations. Alternatively, if none of the candidate regions is confirmed, a genome wide search will be performed, allowing to identify one or more loci for ALS-FTD. The same strategy would then be applied to identify the corresponding gene(s). This project should contribute for identifying the molecular basis of this devastating disorder with practical consequences for genetic counselling in ALS-FTD families, and with the perspective of elucidating the pathophysiology of this disorder.

The objective of this study without direct individual benefit is to confirm the linkage with one or another region of the two identified regions (chromosomes 9 and 15) or to identify a new implicated chromosomal region, and then to reduce the linkage interval in order to identify the responsible gene(s) and characterize the mutations with the study of at least 9 families with FTD and ALS.
Observational Model: Case Control
Time Perspective: Retrospective
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Retention:   Samples With DNA
Whole blood
Non-Probability Sample
Patients and relatives coming in outcome clinics. They are all volunteers and agree to give a blood sample and signing an informed consent explaining the study.
  • Frontotemporal Dementia
  • Amyotrophic Lateral Sclerosis
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  • 1
    Patients with frontotemporal dementia and amyotrophic lateral sclerosis
  • 2
    Relatives (first and second degree) of patients presenting an association of frontotemporal dementia with amyotrophic lateral sclerosis

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
June 2007
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Inclusion Criteria:

  • ALS with FTD, "pure" FTD but with knowledge of relatives with ALS-FTD or "pure" ALS, "pure" ALS but with knowledge of relatives with ALS-FTD or "pure" FTD (not carriers of a mutation in the tau and SOD1 genes), relatives signing the informed consent

Exclusion Criteria:

  • Minors, persons refusing to sign the informed consent
Sexes Eligible for Study: All
18 Years to 90 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
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Isabelle BRINDEL, Department Clinical Research of Developpement
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Alexis Brice, MD Assistance Publique - Hôpitaux de Paris, University Paris 6
Assistance Publique - Hôpitaux de Paris
September 2008