Abstract
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.
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Acknowledgements
We thank the family who participated in this study. We also thank Yasuko Noguchi and Chisa Koga for their technical assistance. This work was supported by a grant for the Initiative on Rare and Undiagnosed Diseases in Pediatrics (no. 18gk0110012h0101) from the Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
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Shimizu, H., Watanabe, S., Kinoshita, A. et al. Identification of a homozygous frameshift variant in RFLNA in a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome. J Hum Genet 64, 467–471 (2019). https://doi.org/10.1038/s10038-019-0581-9
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DOI: https://doi.org/10.1038/s10038-019-0581-9
