Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital scoliosis is a condition characterized by spinal curvature beyond the physiological norm. The molecular mechanisms underlying the pathogenesis of congenital scoliosis are beginning to be clarified; however, the genes related to congenital scoliosis are still unknown. We herein report the results of a comprehensive analysis of gene expression in the spines from a rat model of congenital kyphoscoliosis obtained using DNA microarrays. The rats (Ishibashi rats, IS) showed decreased expression levels of genes associated with bone formation, such as those associated with retinol metabolism and type I collagen. Interestingly, the flexion sites of the IS rats showed low expression levels of tropomyosin receptor kinases (Trks: TrkA, TrkB, and TrkC), which belong to the neurotrophic receptor tyrosine kinase family. Moreover, this phenomenon was observed only in the flexion sites of the spine, and the expression levels of Trks in other parts of the spine in these rats were normal. The decreased expression levels of Trks were observed at both the mRNA and protein levels. We also observed that the number of Trk-immunopositive cells in the lumbar spine in the IS rats was lower than that in wild-type rats. These findings indicate that the Trks have an important function in regulating normal bone formation, and provide a molecular explanation for the pathogenesis of congenital kyphoscoliosis.
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PMID:The Trk family of neurotrophin receptors is downregulated in the lumbar spines of rats with congenital kyphoscoliosis. 2654 52

Specific classes of de novo heterozygous gain-of-function pathogenic variants of the PDGFRB (platelet-derived growth factor receptor-beta) cause a distinctive overgrowth syndrome, named the Kosaki overgrowth syndrome (KOGS) (OMIM #616592). Until now, six patients with this condition have been reported in the literature. In addition to skeletal overgrowth, these patients exhibit hyperelastic, translucent, and fragile skin, scoliosis, progressive loss of subcutaneous adipose tissue, skull deformity, infantile myofibromas, neuropsychiatric symptoms, and arachnoid cysts in the posterior fossa and periventricular white matter signal abnormalities on neuroimaging. This constellation of phenotypes clearly distinguishes KOGS from other PDGFRB-related disorders, including idiopathic basal ganglia calcification, infantile myofibroma, and Penttinen-type premature aging syndrome. From a molecular standpoint, PDGFRB is a dimeric receptor tyrosine kinase that plays critical roles in cell growth and tumorigenesis. The two known types of pathogenic variants (p.(Pro584Arg) and p.(Trp566Arg)) of the PDGFRB that cause KOGS are exclusively located in the juxtaglomerular domain that regulates autoactivation/inhibition of PDGFRB. In-vitro evidence suggests that p.(Pro584Arg) represents a gain-of-function pathogenic variant. Inhibition of PDGFRB activity using multi-kinase inhibitors appears to be a potentially promising therapeutic approach. Investigation of the molecular mechanisms underlying the pathogenesis of this disease using induced pluripotent stem cells is under way. Presence of skeletal overgrowth, distinctive facial features, characteristic hyperelastic and fragile skin, and cerebral white matter lesions with neuropsychiatric symptoms should prompt genetic analysis of the PDGFRB.
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PMID:Kosaki overgrowth syndrome: A newly identified entity caused by pathogenic variants in platelet-derived growth factor receptor-beta. 3171 Jul 79