Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
J Hum Genet. 2019 May;64(5):467-471. doi: 10.1038/s10038-019-0581-9. Epub 2019 Feb 22.
Spondylocarpotarsal synostosis syndrome, a rare syndromic skeletal disorder characterized by disrupted vertebral segmentation with vertebral fusion, scoliosis, short stature, and carpal/tarsal synostosis, has been associated with biallelic truncating mutations in the filamin B gene or monoallelic mutations in the myosin heavy chain 3 gene. We herein report the case of a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome who had a homozygous frameshift mutation in the refilin A gene (RFLNA) [c.241delC, p.(Leu81Cysfs*111)], which encodes one of the filamin-binding proteins. Refilins, filamins, and myosins play critical roles in forming perinuclear actin caps, which change the nuclear morphology during cell migration and differentiation. The present study implies that RFLNA is an additional causative gene for spondylocarpotarsal synostosis syndrome in humans and a defect in forming actin bundles and perinuclear actin caps may be a critical mechanism for the development of spondylocarpotarsal synostosis syndrome.
脊柱足跗骨融合综合征是一种罕见的综合征性骨骼疾病，其特征为椎体分段异常伴椎体融合、脊柱侧凸、身材矮小和腕骨/跗骨融合。该疾病与纤连蛋白 B 基因的双等位基因截断突变或肌球蛋白重链 3 基因的单等位基因突变有关。本文报告了一例脊柱足跗骨融合综合征患者，该患者存在 refilin A 基因（RFLNA）[c.241delC, p.(Leu81Cysfs*111)]纯合移码突变，该基因编码纤连蛋白结合蛋白之一。Refilins、纤连蛋白和肌球蛋白在形成核周肌动蛋白帽中发挥关键作用，在细胞迁移和分化过程中改变核形态。本研究表明，RFLNA 是人类脊柱足跗骨融合综合征的另一个致病基因，形成肌动蛋白束和核周肌动蛋白帽的缺陷可能是脊柱足跗骨融合综合征发生的关键机制。
