title: Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia.
abstract: Achondroplasia (ACH), thanatophoric dysplasia (TD) types I and II, hypochondroplasia (HCH), and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) are all due to activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We review the clinical, epidemiological, radiological, molecular aspects, and signaling pathways involved in these conditions. It is known that FGFR3 signaling is essential to regulate bone growth. The signal transducers and activators of transcription (STAT1) pathway is involved in the inhibition of chondrocyte proliferation, and the mitogen-activated protein kinase (MAPK) pathways are involved in chondrocyte differentiation. Hence, FGFR3 signaling is pivotal in chondrocyte differentiation and proliferation through these two different active pathways. Recent studies on the molecular mechanisms involved in chondrocyte differentiation and proliferation, demonstrated that Snail1 participates in the control of longitudinal bone growth and appears to be essential to transduce FGFR3 signaling during chondrogenesis. This result was confirmed in a newborn infant with TD, and suggests new non-surgical therapeutic approaches, that is, Snail1 as a new encouraging therapeutic target.
authors.affiliation: ECEMC, Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud Carlos III (ISCIII), Sinesio Delgado 6, 28029 Madrid, Spain. mlmartinez.frias@isciii.es
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Frías
authors.forename: Cristina A
authors.initials: CA
authors.lastname: de Frutos
authors.forename: Eva
authors.initials: E
authors.lastname: Bermejo
authors.forename: M Angela
authors.initials: MA
authors.lastname: Nieto
mesh_terms: D000130:Achondroplasia / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D013796:Thanatophoric Dysplasia / Q000235:genetics*