Marfan syndrome (MFS)(OMIM 154700) is a relatively common autosomal dominant genetic disease that causes skeletal, ocular, and cardiovascular defects and was first described by a French pediatrician in 1896 (Bitterman...Marfan syndrome (MFS)(OMIM 154700) is a relatively common autosomal dominant genetic disease that causes skeletal, ocular, and cardiovascular defects and was first described by a French pediatrician in 1896 (Bitterman and Sponseller, 2017). Its prevalence rate is 1/3000—1/5000, and more than 25% of cases are sporadic (Chiu et al., 2014). Studies have shown that about 90% of MFS is caused by variants in the fibrillin-1 gene (FBN1, OMIM 134797). FBN1, located on chromosome 15q21.1, encodes a macromolecular glycoprotein-fibrin 1, which aggregates to form microfibers in the extracellular matrix and distributes in various human connective tissues, such as periosteum, vessel wall, and crystal suspensor ligament. Variants in FNB1 have been reported in 65 exons, but the relationship between genotype and phenotype remains rather unclear (Sakai et al., 2016). Studies have also shown that patients with MFS and similar diseases may have variants in other related genes such as members of the transforming growth factor beta receptor (TGFBR) family (Mizuguchi et al., 2004;Sakai et al., 2006;Bolar et al., 2012;De Cario et al., 2018). For better prevention and treatment of MFS as well as for suspected MFS patients, there is a strong need for efficient genetic testing for early diagnosis and differential diagnoses of patients with related phenotypes (Aubart et al., 2018).展开更多
基金supported by the National Key R&D Program of China (2018YFC1002302, 2016YFC0900103)National Natural Science Foundation of China (81671458)+1 种基金Beijing Lab for Cardiovascular Precision Medicine (PXM2018_014226_000013)supported by the Reproduction Center Biobank at Peking University Third Hospital
文摘Marfan syndrome (MFS)(OMIM 154700) is a relatively common autosomal dominant genetic disease that causes skeletal, ocular, and cardiovascular defects and was first described by a French pediatrician in 1896 (Bitterman and Sponseller, 2017). Its prevalence rate is 1/3000—1/5000, and more than 25% of cases are sporadic (Chiu et al., 2014). Studies have shown that about 90% of MFS is caused by variants in the fibrillin-1 gene (FBN1, OMIM 134797). FBN1, located on chromosome 15q21.1, encodes a macromolecular glycoprotein-fibrin 1, which aggregates to form microfibers in the extracellular matrix and distributes in various human connective tissues, such as periosteum, vessel wall, and crystal suspensor ligament. Variants in FNB1 have been reported in 65 exons, but the relationship between genotype and phenotype remains rather unclear (Sakai et al., 2016). Studies have also shown that patients with MFS and similar diseases may have variants in other related genes such as members of the transforming growth factor beta receptor (TGFBR) family (Mizuguchi et al., 2004;Sakai et al., 2006;Bolar et al., 2012;De Cario et al., 2018). For better prevention and treatment of MFS as well as for suspected MFS patients, there is a strong need for efficient genetic testing for early diagnosis and differential diagnoses of patients with related phenotypes (Aubart et al., 2018).
