Variarfan: Clinical Variability in Marfan Syndrome

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT01707563

Collaborator

Hospices Civils de Lyon (Other), Banque de cellules cochin (Other)

160

Enrollment

Location

Arms

Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Marfan Syndrome	Procedure: skin punch biopsy and molecular biology Other: fibroblast culture and molecular biology	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

160 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: Marfan patients Study participants were recruited between 11/2009 and 10/2011, among adult patients consulting in the Multidisciplinary Marfan Clinic of our University Hospital, and having a known mutation in the FBN1 gene. There, patients are evaluated by geneticists, rheumatologists, cardiologists, and ophthalmologists. Systematic slit-lamp examination, cardiac ultrasonography, and radiological investigations are also performed. A skin punch biopsy was used to establish a fibroblast cell culture. We determined mRNA levels for FBN1 and compared it to the clinical involvement.	Procedure: skin punch biopsy and molecular biology
Other: control patients Fibroblasts were obtained from non Marfan patients (cell bank). We determineed mRNA level for FBN1 for each allele.	Other: fibroblast culture and molecular biology

Arm

Intervention/Treatment

Other: Marfan patients

Study participants were recruited between 11/2009 and 10/2011, among adult patients consulting in the Multidisciplinary Marfan Clinic of our University Hospital, and having a known mutation in the FBN1 gene. There, patients are evaluated by geneticists, rheumatologists, cardiologists, and ophthalmologists. Systematic slit-lamp examination, cardiac ultrasonography, and radiological investigations are also performed. A skin punch biopsy was used to establish a fibroblast cell culture. We determined mRNA levels for FBN1 and compared it to the clinical involvement.

Procedure: skin punch biopsy and molecular biology

Other: control patients

Fibroblasts were obtained from non Marfan patients (cell bank). We determineed mRNA level for FBN1 for each allele.

Other: fibroblast culture and molecular biology

Outcome Measures

Primary Outcome Measures

FBN1 expression level [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre de Reference Maladie de Marfan Et Apparente	Paris	Ile de France	France	75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris
Hospices Civils de Lyon
Banque de cellules cochin

Investigators

Principal Investigator: Chantal Stheneur, PHD, MD, Hôpital Bichat, AP-HP

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT01707563

Other Study ID Numbers:

P071009

First Posted:

Oct 16, 2012

Last Update Posted:

Nov 6, 2014

Last Verified:

Dec 1, 2010

Keywords provided by Assistance Publique - Hôpitaux de Paris

Additional relevant MeSH terms:

Marfan Syndrome

Arachnodactyly

Syndrome

Study Results

No Results Posted as of Nov 6, 2014