A 45-year-old Italian male with p.(Gly1815Ser) FBN1 mutation causing a mild variant of Marfan syndrome: A case study

A 45-year-old Italian male was referred as suspected of having a heritable connective tissue disorders by clinical findings, including joint hyperlaxity and soft, smooth, velvety, and slightly elastic skin. Using a specific custom panel including genes involved in these disorders, next-generation sequencing (NGS) analysis led to the identification of the c. 5443G>A, p.(Gly1815Ser), (rs745680336) variant in fibrillin-1 (FBN1) gene, encoding the FBN1. Mutations in this protein are responsible for different connective tissue disorders, collectively known as type 1 fibrillinopathies, including Marfan syndrome (MFS). Multiple sequencing alignment of human FBN1 protein with various species revealed that the mutation occurred within a highly conserved region of the calcium-binding epidermal growth factor-like domain and affected the protein structure/function, suggesting its pathogenic role. NGS techniques successfully identified the molecular defect in this patient, clinically resembling as MFS, even if a clear genotype-phenotype correlation remains still challenging.