Undescribed mutations in FBN1 gene in two family cases of Marfan syndrome.

ABSTRACT

Marfan syndrome (MFS) is a multisystem autosomal dominant heritable disorder and, although there are over 1700 mutations that have been identified in the fibrillin-1 (FBN1) gene associated with it, there are many variants that remain unknown. Here we report two family cases of MFS with two new undescribed variations (C914S and H2426C) in FBN1 gene. Both variations produce alterations in the structural conformation of the protein resulting in pathogenic events in these patients. Finally, this case report includes both pathogenic mutations that have also been clinically and genetically confirmed to result in MFS. This clinical, genetic, and in silico analysis of potentially harmful variations in unrelated MFS patients provides additional evidence for the suggested causative role of the mutations c.2740T > A (C914S), c.7276_7278delCAT (p.H2426C) in FBN1 gene in MFS. <Learning objective: New previously undescribed mutations in fibrillin-1 (FBN1) gene related to Marfan syndrome (MFS) have been confirmed by genetic, bioinformatics, and clinical studies. It is well known that MFS is caused by mutations in FBN1 gene; however many of them remain unknown. These data could be relevant in the screening of these patients offering a different follow-up by considering these and other genetic mutations. These types of mutations should be considered in differential diagnosis.>.