Clinical Trial: Clinical Variability in Marfan Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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.


Detailed 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 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.


Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: FBN1 expression level [ Time Frame: 6 months ]

Evaluation in Marfan patients, of FBN1 expression level (non-mutated or mutated allele) compared to the clinical expression of the disease in idividuals


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: October 12, 2012
Date Started: January 2009
Date Completion:
Last Updated: November 5, 2014
Last Verified: December 2010