[Molecular genetics of congenital skeletal dysplasias related to mutations of fibroblast growth factor receptors].
Fibroblast growth factor receptors belong to the family of a membrane bound tyrosine kinases, which respond to stimulation by the fibroblast growth factor family of cytokines. Signalling through fibroblast growth factor receptors regulates proliferation and differentiation of connective tissue cells. Disruption of these important processes during morphogenesis results in skeletal dysplasias. Mutations of the fibroblast growth factor receptors (1, 2 and 3) cause achondroplasia, Crouzon syndrome and Apert syndrome, which are amongst the most common congenital dysmorphic syndromes. There exists a correlation between the genotype and phenotype in fibroblast growth factor receptors related syndromes. This relation can be explained on the basis of molecular pathology of the receptor protein. An increased frequency of new mutations and exclusive paternal origin of mutated alleles is explained by the role of fibroblast growth factor signalling during spermatogenesis. The availability of molecular tests for fibroblast growth factor receptors related syndromes should facilitate the diagnostic accuracy of these pleiotropic diseases which is independent of expression variability.
II Katedra Chorób Wewnetrznych Collegium Medicum Uniwersytetu Jagiellońskiego w Krakowie.
M
M
Sanak
D001848:Bone Diseases, Developmental / Q000175:diagnosis / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*
D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2