Filamin B （FLNB） is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure. Lip to present, pathogenic mutations in FLNB are solely found to cause skeletal defor...Filamin B （FLNB） is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure. Lip to present, pathogenic mutations in FLNB are solely found to cause skeletal deformities, indicating the important role of FLNB in skeletal development. FLNB-related disorders are classified as spondylocarpotarsal synostosis （SCT）, Larsen syndrome （LS）, atelosteogenesis （AO）, boomerang dysplasia （BD）, and isolated congenital talipes equinovarus, presenting with scoliosis, short- limbed dwarfism, clubfoot, joint dislocation and other unique skeletal abnormalities. Several mecha- nisms of FLNB mutations causing skeletal malformations have been proposed, including delay of ossi- fication in long bone growth plate, reduction of bone mineral density （BMD）, dysregulation of muscle differentiation, ossification of intervertebral disc （IVD）, disturbance of proliferation, differentiation and apoptosis in chondrocytes, impairment of angiogenesis, and hypomotility of osteoblast, chondrocyte and fibroblast. Interventions on FLNB-related diseases require prenatal surveillance by sonography, gene testing in high-risk carriers, and proper orthosis or orthopedic surgeries to correct malformations including scoliosis, cervical spine instability, large joint dislocation, and clubfoot. Gene and cell therapies for FLNB-related diseases are also promising but require further studies.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81501852,81472046 and 81472045)the Beijing Natural Science Foundation(No.7172175)+6 种基金the Beijing nova program(No.2161100004916123)the Beijing nova program interdisciplinary collaborative project(No.xxjc201717)the 2016 Milstein Medical Asian American Partnership Foundation Fellowship Award in Translational Medicine,the Central Level Public Interest Program for Scientific Research Institute(No.2016ZX310177)the PUMC Youth Fund&the Fundamental Research Funds for the Central Universities(No.3332016006)the CAMS Initiative for Innovative Medicine(No.2016-12M-3-003)the Distinguished Youth foundation of Peking Union Medical College Hospital(No.JQ201506)the National Key Research and Development Program of China(No.2016YFC0901501)
文摘Filamin B （FLNB） is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure. Lip to present, pathogenic mutations in FLNB are solely found to cause skeletal deformities, indicating the important role of FLNB in skeletal development. FLNB-related disorders are classified as spondylocarpotarsal synostosis （SCT）, Larsen syndrome （LS）, atelosteogenesis （AO）, boomerang dysplasia （BD）, and isolated congenital talipes equinovarus, presenting with scoliosis, short- limbed dwarfism, clubfoot, joint dislocation and other unique skeletal abnormalities. Several mecha- nisms of FLNB mutations causing skeletal malformations have been proposed, including delay of ossi- fication in long bone growth plate, reduction of bone mineral density （BMD）, dysregulation of muscle differentiation, ossification of intervertebral disc （IVD）, disturbance of proliferation, differentiation and apoptosis in chondrocytes, impairment of angiogenesis, and hypomotility of osteoblast, chondrocyte and fibroblast. Interventions on FLNB-related diseases require prenatal surveillance by sonography, gene testing in high-risk carriers, and proper orthosis or orthopedic surgeries to correct malformations including scoliosis, cervical spine instability, large joint dislocation, and clubfoot. Gene and cell therapies for FLNB-related diseases are also promising but require further studies.
