Analysis of genetic heterogeneity in Marfan Syndrome (MFS)

• Grant number: 05/03170-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2006
• End date: August 31, 2009
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Lygia da Veiga Pereira
• Grantee: Lúcia Valéria da Silva Teixeira Machado
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Marfan syndrome (MS) (MIM=15470) is a conective tissue disease of autossomal dominant inheritance, with clinical variability intra and inter familial, and no predilection for race or sex, that shows a prevalence of 1/10.000 individuals. Aproximately 30% of the cases are sporadical and the remain inherited the clinical manifestations are concetrated in three main systems: skeletal, cardiovascular and ocular. Mutations in gene FBN1 (15q21, 65 exons) that codifies the fibrilina protein, main strutural component of microfibers, causes the MS. Until the moment, approximately 300 mutations in gene FBN1 had been detected in patients with MS. However it only corresponds to 10-15% of the waited mutations, suggesting a low level of detention mutation or genetic heterogenty in the MS. Recently DHPLC was applied to the detention of mutations in more than 50 genes it had been used for FBN1 many times, showing rate mutation of detention that varies of 80-95%. Another intresting gene fact was the study of another locus for the MS in a great French family in 3p25-p24.2. The clinical findings aparently are similar and the chromosomic study in a Japanese petient with MS showed a reciprocal translocation involving 3p24.1 breaking point modifies the coding region of receiver 2 TGF-beta gene. A mutation in a splicing site was found in this great Frenhc family, proving the existence of the genetic heterogenity in the MS. The discovery of mutations in this gene in other syndromes with very similar clinical findings to the one of the SMF, as the Syndrome of Loeys-Dietz, became the question of the genetic heterogeneidade a question of basic importance in the diagnosis and prognostic of the MF.