[From gene to disease; achondroplasia and other skeletal dysplasias due to an activating mutation in the fibroblast growth factor].
Achondroplasia, the most common and best known skeletal dysplasia, is inherited in an autosomal dominant fashion. Like a number of other skeletal dysplasias, among which hypochondroplasia and thanatophoric dysplasia, achondroplasia is caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. FGFR3 is a negative regulator of bone growth. Binding of fibroblast growth factors to the FGFR3 receptor stimulates its tyrosine kinase activity in the cell. This activates a signal transduction pathway that regulates enchondral ossification by inhibition of cell division and stimulation of cell maturation and differentiation. Mutations in the FGFR3 gene give rise to activation of the receptor in the absence of growth factors, thus causing abnormal long bone development. Position and type of mutation in the FGFR3 gene determine the extent of overactivation and thus the severity of the skeletal abnormality.
van Ravenswaaij-Arts
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Universitair Medisch Centrum St Radboud, afd. Antropogenetica, Postbus 9101, 6500 HB Nijmegen. c.vanravenswaay@antrg.azn.nl
Losekoot
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D000130:Achondroplasia / Q000453:epidemiology / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D010009:Osteochondrodysplasias / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D011859:Radiography; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013796:Thanatophoric Dysplasia / Q000000981:diagnostic imaging / Q000235:genetics*
D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3