Study of de novo TGFBR2 gene mutation in type 2 Marfan syndrome

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Objective To report the clinical features and the screening results of the pathogenic gene in two type 2 Marfan syndrome families, and to explore the relationship between the transmembrane domain of transforming growth factor beta receptor Ⅱ (TGFBR2) gene and the clinical phenotype. Methods The FBN1 and TGFBR2 genes were sequenced in the genome DNA of type 2 Marfan syndrome probands and pedigrees, and the protein structure prediction of the TGFBR2 gene transmembrane domain missense mutation and genotype-phenotype analysis were performed. Results The two probands were diagnosed as type 2 Marfan syndrome patients.Two de novo TGFBR2 gene missense mutations p. I37K(c.110T>A) and p. G43D(c.128G>A) were found in the probands and family members.The TGFBR2 gene missense mutations changed the protein conformation of the transmembrane domain and disturbed the protein structure and function of TGFBR2.Genotype-phenotype analysis found that all the transmembrane domain missense mutation carriers had major cardiovascular involvement. Conclusions This study reports two de novo TGFBR2 gene mutations p. I37K and p. G43D located at the transmembrane domain, which are more likely to occur in patients with serious cardiovascular diseases such as aortic dilatation and aortic dissection.This is of great significance for gene tic testing, diagnosis and treatment of type 2 Marfan syndrome and other related diseases associated with transforming growth factor-β pathway. Key words: Marfan syndrome; Transforming growth factor beta receptor Ⅱ gene; Gene mutation; Transforming growth factor beta pathway related diseases; Genotype-phenotype study