A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome

作者：Toydemir Reha M; Brassington Anna E; Bayrak Toydemir Pinar; Krakowiak Patrycja A; Jorde Lynn B; Whitby Frank G; Longo Nicola; Viskochil David H; Carey John C; Bamshad Michael J^*

来源：American Journal of Human Genetics, 2006, 79(5): 935-941.

DOI：10.1086/508433

Activating mutations of FGFR3, a negative regulator of bone growth, are well known to cause a variety of short-limbed bone dysplasias and craniosynostosis syndromes. We mapped the locus causing a novel disorder characterized by camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL syndrome) to chromosome 4p. Because this syndrome recapitulated the phenotype of the Fgfr3 knockout mouse, we screened FGFR3 and subsequently identified a heterozygous missense mutation that is predicted to cause a p.R621H substitution in the tyrosine kinase domain and partial loss of FGFR3 function. These findings indicate that abnormal FGFR3 signaling can cause human anomalies by promoting as well as inhibiting endochondral bone growth.

• 出版日期2006-11