Clinical trial NCT02870127: Clinical Investigation and Molecular Forms of Family Disease of Varicose
Official title: Genetic Study of Varicose Disease by Sequencing Exome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Varicose Veins
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre de Soins
First posted: 2016-08-17
Enrollment: 430
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The initial step of this protocol relies on recruiting large families (\> 8 met) for a genetic linkage analysis. It consists firstly in identifying patients with varicose veins occurring in a family context, and to conduct a comprehensive survey to assess the potentially informative family (significant number of individuals with multiple generations) and ensure their membership prior to the study. The next step is the fine and accurate phenotyping of each of the family members and the collection of a blood sample for DNA extraction for molecular genetic analysis (family linkage analysis and sequencing exome ).

Brief summary: The existence of a family factor in the genesis of varicose veins is certain, but few studies have addressed reliably instead of the genetic factor in clinical and molecular level. The investigator initiated an original study to identify one or more genetic abnormalities predisposing to varicose disease, based on a combined approach of genetic linkage and of exome sequencing. The clinical research phase is an essential prerequisite to the identification of genetic mutations; it is to identify large affected families and ensure an extremely rigorous and accurate phenotyping of individuals over several generations. A first clinical work has identified and / or phenotype 8 families with a genetically informative family suggesting autosomal dominant inheritance. Linkage analysis suggested several candidate chromosomal regions without allowing the identification of a gene. This project aims to resume and expand the Family clinical investigations and apply the techniques of genome analysis points, including exome sequencing on the most informative families to identify the genes and mechanisms responsible of this disease and improve the prevention and the treatment of varicose veins.


Eligibility criteria: Inclusion Criteria:

* Any patient consultant the Medicine Vascular Surgery for varicose veins of the lower limbs as part of a manifesto family context
* Varices Presence in at least one family member
* Written consent

Exclusion Criteria:

* Patients who are unable to sign or who refuse to sign an informed consent
* Subjects aged less than 25 years, due to the low penetrance of varicose disease that age.
* Secondary veins at a post-thrombotic disease (suspected by the examination and confirmed by Doppler ultrasonography of the deep venous system)
* Venous angiodysplasia or secondary varicose arteriovenous fistulas.

Primary outcomes:
measure: genetic abnormalities segregating with the presence of varicose veins in the informative families recruited.
timeFrame: year 4
Secondary outcomes:
measure: genotype/phenotype relationship
timeFrame: year 4
Other outcomes:
Locations:
city: La Roche sur Yon
country: France
facility: La Roche sur Yon Hospital
city: Nantes
country: France
facility: Nantes Univesrity Hospital
Study officials:
affiliation: Nantes University Hospital
name: Marc-Antoine Pistorius, PU-PH
role: PRINCIPAL_INVESTIGATOR
References: