Clinical Variability in Marfan Syndrome
Clinical Variability in Marfan Syndrome
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.
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.
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.