Ignite Creation Date:
2024-05-05 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00159198
Status:
TERMINATED
Last Update Posted:
2008-09-08
First Post:
2005-09-07
Brief Title:
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Genetic Linkage in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Status:
TERMINATED
Status Verified Date:
2008-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Completed
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 andor 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 genes will be identified it will then possible to define its spectrum of mutations and to establish genotypephenotype 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 genes 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
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 genes will be identified it will then possible to define its spectrum of mutations and to establish genotypephenotype 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 genes 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
Detailed Description:
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 genes and characterize the mutations with the study of at least 9 families with FTD and ALS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P011023 | None | None | None |