Thus, this study identifies a novel inhibitory peptide for FGFR3 signaling, which may serve as a potential therapeutic agent for the treatment of FGFR3-related skeletal dysplasia.
In this communication, we report the identification of a mosaic R248C missense mutation in the IgII-III linker region of the gene encoding the fibroblast growth factor receptor-3 (FGFR3), in an individual who manifests a skeletal dysplasia and epidermal hyperplasia.
We have identified a novel fibroblast growth factor receptor 3 (FGFR3) missense mutation in four unrelated individuals with skeletal dysplasia that approaches the severity observed in thanatophoric dysplasia type I (TD1).
Our results extend the genetic mutation spectrum of FGFR3 and demonstrate that TES is an effective method for the diagnosis of skeletal dysplasia in clinical practices.
Other mutations within the FGFR3 tyrosine kinase domain (e.g., C1620A or C1620G [both resulting in Asn540Lys]) are known to cause hypochondroplasia, a relatively common but milder skeletal dysplasia.
The pathology of small hypertrophic chondrocytes due to up-regulated FGFR3 signaling in FGFR3skeletal dysplasia was recapitulated in growth plate cartilage formed in the xenografts of patient-specific hiPSC-derived cartilage.
A large proportion of these tumors (39%) harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms.
In this review, we describe the mechanisms of potential therapeutic targets and underlying regulators and then systematically review molecular therapeutic strategies for FGFR3 gene-related skeletal dysplasia based on current knowledge.
Our results extended the mutational spectrum of FGFR3 and proved that applications of NGS and bioinformatics are effective methods for skeletal dysplasia diagnosis in clinical practices.
Activating mutations of the FGFR3 gene lead to craniosynostosis and multiple types of skeletal dysplasia with varying degrees of severity: thanatophoric dysplasia (TD), achondroplasia and hypochondroplasia.
We describe the first case of protein-losing enteropathy in a pediatric patient, with severe skeletal dysplasia consistent with thanatophoric dysplasia type I and DNA analysis that revealed a c.1949A>T (p.Lys650Met) in exon 15 of the FGFR3 gene.
Heterozygous mutation of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with extensive skeletal dysplasia and abnormality of tooth growth.
Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia due to mutations causing haploinsufficiency of RUNX2, an osteoblast transcription factor specific for bone and cartilage.
Cleidocranial dysplasia (CCD) is a rare autosomal-dominantly inherited skeletal dysplasia that is predominantly associated with heterozygous mutations of RUNX2.
In this review, we divide the osteochondrodysplasias into groups based on their genetic relationships, including mutations in various types of collagen, fibroblast growth factor, cartilage oligomeric matrix protein, parathyroid hormone receptor, the diastrophic dysplasia sulfate transporter, enzymes such as steroid sulfatases, transcription factor SOX9, and a cysteine proteinase, cathepsin K. We describe the major osteochondrodysplasias, define their causes and clinical manifestations, and provide the orthopaedic surgeon with an understanding of the underlying molecular defects as well as the anatomical aspects of these disorders.
In this review, we divide the osteochondrodysplasias into groups based on their genetic relationships, including mutations in various types of collagen, fibroblast growth factor, cartilage oligomeric matrix protein, parathyroid hormone receptor, the diastrophic dysplasia sulfate transporter, enzymes such as steroid sulfatases, transcription factor SOX9, and a cysteine proteinase, cathepsin K. We describe the major osteochondrodysplasias, define their causes and clinical manifestations, and provide the orthopaedic surgeon with an understanding of the underlying molecular defects as well as the anatomical aspects of these disorders.
Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3.