Filamin B: The next hotspot in skeletal research?

Qiming Xu; Nan Wu; Lijia Cui; Zhihong Wu; Guixing Qiu

doi:10.1016/j.jgg.2017.04.007

Volume 44 Issue 7

Jul. 2017

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Article Navigation > Journal of Genetics and Genomics > 2017 > 44(7): 335-342

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Filamin B: The next hotspot in skeletal research?

doi: 10.1016/j.jgg.2017.04.007

Qiming Xu^{a, #},
Nan Wu^{a, b, c, #},
Lijia Cui^{d, e},
Zhihong Wu^{b, c, f},
Guixing Qiu^{a, b, c}

a
Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
b
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China
c
Medical Research Center of Orthopaedics, Chinese Academy of Medical Sciences, Beijing 100730, China
d
Peking Union Medical College Hospital, Beijing 100730, China
e
School of Medicine, Tsinghua University, Beijing 100084, China
f
Department of Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China

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Corresponding author: E-mail address: qiuguixingpumch@126.com (Guixing Qiu)
Received Date: 2017-02-21
Accepted Date: 2017-04-12
Rev Recd Date: 2017-03-15

Available Online: 2017-07-06

Publish Date: 2017-07-20

Abstract

Abstract

Filamin B (FLNB) is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure. Up 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 mechanisms of FLNB mutations causing skeletal malformations have been proposed, including delay of ossification 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.
- Filamin B,
- Spondylocarpotarsal synostosis,
- Larsen syndrome,
- Scoliosis,
- Skeletal development

These authors contributed equally to this work.

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References(66)

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