Filamin B： The next hotspot in skeletal research

• Published in: Journal of genetics and genomics Vol. 44; no. 7; pp. 335 - 342
• Main Authors: Xu, Qiming, Wu, Nan, Cui, Lijia, Wu, Zhihong, Qiu, Guixing
• Format: Journal Article
• Language: English
• Published: China Elsevier Ltd 20.07.2017
• Subjects: abnormal development; angiogenesis; Animals; apoptosis; bone density; bone formation; cervical spine; chondrocytes; crosslinking; Disease; dwarfing; fibroblasts; filamin; Filamin B; Filamins - chemistry; Filamins - genetics; Filamins - metabolism; genes; growth plate; Humans; intervertebral disks; Larsen syndrome; microfilaments; monitoring; muscles; Mutation; orthopedics; osteoblasts; Scoliosis; Skeletal development; Skeleton - cytology; Skeleton - metabolism; Skeleton - pathology; Spondylocarpotarsal synostosis; surgery; tarsus (bone); ultrasonography; 治疗方法; 疾病; 细胞疗法; 肌动蛋白; Spondylocarpotarsal synostosis; Skeletal development; Scoliosis; Larsen syndrome; Filamin B
• DOI: 10.1016/j.jgg.2017.04.007
• ISSN: 1673-8527

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.