Clinical trial NCT01707563: Clinical Variability in Marfan Syndrome
Official title: Correlations' Study Between Variability of Expression in FBN1 Gene and Clinical Features in Marfan Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Marfan Syndrome
Keywords: Marfan syndrome
Variability
Fibrillin 1
clinical expression
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Hospices Civils de Lyon
name: Banque de cellules cochin
First posted: 2012-10-16
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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 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 criteria: 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.

Primary outcomes:
measure: FBN1 expression level
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre de Reference Maladie de Marfan Et Apparente
state: Ile de France
Study officials:
affiliation: Hôpital Bichat, AP-HP
name: Chantal Stheneur, PHD, MD
role: PRINCIPAL_INVESTIGATOR
References: