NCT01707563

Clinical Variability in Marfan Syndrome

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 160 (actual)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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 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.

Conditions

• Marfan Syndrome

Interventions

Type	Name	Description
PROCEDURE	skin punch biopsy and molecular biology
OTHER	fibroblast culture and molecular biology

Timeline

• Start date: 2009-01-01
• Primary completion: 2011-06-01
• Completion: 2012-01-01
• First posted: 2012-10-16
• Last updated: 2014-11-06

Locations

1 site across 1 country: France