Clinical Variability in Marfan Syndrome

Marfan Syndrome Clinical Trial

— Variarfan  

Official title:

Correlations' Study Between Variability of Expression in FBN1 Gene and Clinical Features in Marfan Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01707563
• Other study ID #: P071009
• Status: Completed
• Phase: N/A
• First received: October 12, 2012
• Last updated: November 5, 2014
• Start date: January 2009
• Est. completion date: January 2012

Study information

• Verified date: December 2010
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in the fibrillin-1 gene (FBN1). Penetrance of FBN1 mutations is complete but intra and inter familial clinical expressivity is extremely variable. The underlying mechanisms for variability are not understood. An interesting mechanism is that the expression level of the wild type and/or mutated allele may play a role in the determination of variability.

Principal objective: To evaluate in Marfan patients, if FBN1 expression level (non-mutated or mutated allele) modulates the clinical expression of the disease.

Judgment criteria : Correlation allelic expression level-phenotype Perspectives : To search the predictive factors of severity in order to ameliorate precocity of taking care.

Description:

Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in the fibrillin-1 gene (FBN1). Penetrance of FBN1 mutations is complete but intra and inter familial clinical expressivity is extremely variable. The underlying mechanisms for variability are not understood. An interesting mechanism is that the expression level of the wild type and/or mutated allele may play a role in the determination of variability.

Principal objective : To evaluate in Marfan patients, if FBN1 expression level (non-mutated or mutated allele) modulates the clinical expression of the disease in individuals from families with clinical variability (intrafamilial) and in independant probands (interfamilial).

Judgment criteria : Correlation allelic expression level-phenotype Method : In Marfan patients with a FBN1 nul allele, FBN1 RNA will be extracted from a fibroblast culture. Allelic FBN1 expression level will be performed by quantitative RT-PCR and then compared with clinical evaluation.

Number of subjects : 160 subjects, 45 Marfan patients in 15 independent families, 5 patients with the same mutation, 30 with a private mutation leading to a nul allele and 80 non Marfan subjects.

Perspectives : To search the predictive factors of severity in order to ameliorate precocity of taking care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: January 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Man or woman > 18 years old

• With a mutation in FBN1 gene

• Has signed an informed consent form

Exclusion Criteria:

-No affiliated to a Healthcare System.

Study Design

Allocation: Non-Randomized, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Marfan Syndrome

Intervention

Procedure:
• skin punch biopsy and molecular biology

Other:
• fibroblast culture and molecular biology

Locations

Country	Name	City	State
France	Centre de Reference Maladie de Marfan Et Apparente	Paris	Ile de France

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Banque de cellules cochin, Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FBN1 expression level	Evaluation in Marfan patients, of FBN1 expression level (non-mutated or mutated allele) compared to the clinical expression of the disease in idividuals	6 months	No