Identification of a homozygous frameshift variant in RFLNA in a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome.

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.

• Authors: Hitomi Shimizu, Satoshi Watanabe, Akira Kinoshita, Hiroyuki Mishima, Gen Nishimura, Hiroyuki Moriuchi, Koh-Ichiro Yoshiura, Sumito Dateki
• Journal: Journal of human genetics (J Hum Genet) Vol. 64 Issue 5 Pg. 467-471 (May 2019) ISSN: 1435-232X [Electronic] England
• PMID: 30796325 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Microfilament Proteins
• RFLNA protein, human

Topics

• Abnormalities, Multiple (genetics, metabolism, pathology)
• Biomarkers, Tumor (genetics, metabolism)
• Frameshift Mutation
• Homozygote
• Humans
• Infant
• Lumbar Vertebrae (abnormalities, metabolism, pathology)
• Male
• Microfilament Proteins
• Musculoskeletal Diseases (genetics, metabolism, pathology)
• Scoliosis (congenital, genetics, metabolism, pathology)
• Synostosis (genetics, metabolism, pathology)
• Thoracic Vertebrae (abnormalities, metabolism, pathology)