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Mutation in FKBP10 causes early onset of scoliosis

ABSTRACT: Scoliosis is a three-dimensional structural deformity of the spine, while the underlying pathogenesis is not fully uncovered. Osteogenesis imperfecta (OI), known as brittle bone disease, is a group of rare genetic disorder associated with osteopenia, deformity and scoliosis. Here we found the mutation in FKBP10 resulted in early onset of scoliosis via deleterious effects on collagen processing and osteoblast differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180838 | GEO | 2024/07/01

REPOSITORIES: GEO

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Trancsriptomic analyses reveal aberrant differentiation trajectory with WNT1 Loss-of-Function in type XV osteogenesis imperfecta

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Multi-Omic analyses reveal aberrant differentiation trajectory with WNT1 Loss-of-Function in type XV osteogenesis imperfecta

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A Progeroid Syndrome with Severe Osteogenesis Imperfecta segregates with an Intronic TAPT1 homozygous Variant that Creates a knockout allele [RNA-seq]

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Cytoskeletal Keratins Are Overexpressed in a Zebrafish Model 2 of Idiopathic Scoliosis

Project description:Idiopathic scoliosis (IS) is a three-dimensional rotation of the spine >10 degrees with an unknown etiology. Our laboratory established a late-onset IS model in zebrafish (Danio rerio) containing a deletion in kif7. 25% of kif7co63/co63 zebrafish develop spinal curvatures and are otherwise developmentally normal, although the molecular mechanisms underlying the scoliosis are unknown. To define transcripts associated with scoliosis in this model, we performed bulk mRNA sequencing on 6 weeks past fertilization (wpf) kif7co63/co63 zebrafish with and without scoliosis. Additionally, we sequenced kif7co63/co63, kif7co63/+, and AB zebrafish (n= 3 per genotype). Sequencing reads were aligned to the GRCz11 genome and FPKM values were calculated. Differences between groups were calculated for each transcript by t-test. Principal component analysis showed that transcriptomes clustered by sample age and genotype. kif7 mRNA was mildly reduced in both homozygous and heterozygous zebrafish compared to AB. Sonic hedgehog target genes were upregulated in kif7co63/co63 zebrafish over AB, but no difference was detected between scoliotic and non-scoliotic mutants. The top upregulated genes in scoliotic zebrafish were cytoskeletal keratins.. Pankeratin staining of 6 wpf scoliotic and non-scoliotic kif7co63/co63 zebrafish showed increased keratin levels within the zebrafish musculature and intervertebral disc (IVD). Keratins are major components of the embryonic notochord, and aberrant keratin expression has been associated with intervertebral disc degeneration (IVDD) in both zebrafish and humans. The role of increased keratin accumulation as a molecular mechanism associated with the onset of scoliosis warrants further study.

2023-05-03 | GSE231606 | GEO

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