RELATIONSHIP OF THE TYPE AND POSITION OF MUTATION IN THE FBN1 GENE WITH CLINICAL MANIFESTATIONS OF MARFAN SYNDROME IN CHILDREN

Marfan syndrome (OMIM # 154700) is an inherited connective tissue disease caused by mutations in the FBN1 gene, characterized by marked clinical variability, the causes of which are poorly understood. The aim of this study was to determine the association of the type and localization of the FBN1 gene mutation with the severity of clinical manifestations of Marfan syndrome in a Russian cohort of children. Results: for the first time in a Russian cohort of children, the association between the type and localization of the FBN1 gene mutation and the severity of clinical manifestations was demonstrated: LoF mutations lead to greater damage to the cardiovascular and skeletal systems; missense mutations lead to greater damage to the eyes. Mutations in exons 1-10 lead to the earliest onset of skeletal changes (foot (p=0.016) and chest (p=0.036) deformities), mutations in exons 11-20-to the earliest appearance of lens ectopia (p=0.034), with less severe dolichostenomelia (p=0.041) and less frequent formation of aortic dilatation (p=0.035). Mutations in exons 21-35 are accompanied by the earliest manifestation of spinal deformity (p=0.02). Mutations in exons 51-66 less often lead to lens ectopia (p=0.001).