Clinical Variability in Marfan Syndrome

NCT01707563 | Completed

• 1 other identifier: P071009
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

Marfan Syndrome

Keywords

Marfan syndrome; Variability; Fibrillin 1; clinical expression

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Marfan patients

OTHER

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

control patients

OTHER

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

Other: fibroblast culture and molecular biology

Interventions

skin punch biopsy and molecular biology PROCEDURE

Marfan patients

fibroblast culture and molecular biology OTHER

control patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman \> 18 years old
• With a mutation in FBN1 gene
• Has signed an informed consent form

You may not qualify if:

• No affiliated to a Healthcare System.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Hospices Civils de Lyon: collaborator
• Banque de cellules cochin: collaborator

Study Sites (1)

Centre de Reference Maladie de Marfan Et Apparente

Paris, Île-de-France Region, 75018, France

Location

MeSH Terms

Conditions

Marfan Syndrome; Arachnodactyly

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Limb Deformities, Congenital; Musculoskeletal Abnormalities

Study Officials

• Chantal Stheneur, PHD, MD

  Hôpital Bichat, AP-HP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2012
• First Posted: October 16, 2012
• Study Start: January 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: January 1, 2012
• Last Updated: November 6, 2014

Record last verified: 2010-12

Locations

FR (1)