Clinical Variability in Marfan Syndrome (Variarfan)
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Purpose
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 | Intervention |
|---|---|
| Marfan Syndrome | Procedure: skin punch biopsy and molecular biology Other: fibroblast culture and molecular biology |
| Study Type: | Interventional |
| Study Design: | 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. |
- 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
| Enrollment: | 160 |
| Study Start Date: | January 2009 |
| Study Completion Date: | January 2012 |
| Primary Completion Date: | June 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
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Procedure: skin punch biopsy and molecular biology |
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control patients
Fibroblasts were obtained from non Marfan patients (cell bank). We determineed mRNA level for FBN1 for each allele.
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Other: fibroblast culture and molecular biology |
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.
Eligibility
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01707563
| France | |
| Centre de Reference Maladie de Marfan Et Apparente | |
| Paris, Ile de France, France, 75018 | |
| Principal Investigator: | Chantal Stheneur, PHD, MD | Hôpital Bichat, AP-HP |
More Information
| Responsible Party: | Assistance Publique - Hôpitaux de Paris |
| ClinicalTrials.gov Identifier: | NCT01707563 History of Changes |
| Other Study ID Numbers: |
P071009 |
| First Submitted: | October 12, 2012 |
| First Posted: | October 16, 2012 |
| Last Update Posted: | November 6, 2014 |
| Last Verified: | December 2010 |
Keywords provided by Assistance Publique - Hôpitaux de Paris:
|
Marfan syndrome Variability Fibrillin 1 clinical expression |
Additional relevant MeSH terms:
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Marfan Syndrome Arachnodactyly Syndrome Disease Pathologic Processes Bone Diseases, Developmental Bone Diseases Musculoskeletal Diseases Heart Defects, Congenital |
Cardiovascular Abnormalities Cardiovascular Diseases Heart Diseases Abnormalities, Multiple Congenital Abnormalities Genetic Diseases, Inborn Connective Tissue Diseases Limb Deformities, Congenital Musculoskeletal Abnormalities |