A Novel Mutation in FGFR3 Causes Camptodactyly, Tall Stature, and Hearing Loss (CATSHL) Syndrome

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 syndrom...

Full description

Saved in:
Bibliographic Details
Published in:American journal of human genetics 2006-11, Vol.79 (5), p.935-941
Main Authors: Toydemir, Reha M., Brassington, Anna E., Bayrak-Toydemir, Pınar, Krakowiak, Patrycja A., Jorde, Lynn B., Whitby, Frank G., Longo, Nicola, Viskochil, David H., Carey, John C., Bamshad, Michael J.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acid Substitution
Animals
Base Sequence
Biological and medical sciences
Bone Diseases, Developmental - genetics
Bones
Diseases of the osteoarticular system
DNA - genetics
Female
Fingers - abnormalities
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genetics of eukaryotes. Biological and molecular evolution
Genotype & phenotype
Hearing loss
Hearing Loss, Bilateral - genetics
Hearing Loss, Sensorineural - genetics
Heterozygote
Humans
Male
Malformations and congenital and or hereditary diseases involving bones. Joint deformations
Medical genetics
Medical sciences
Mice
Mice, Knockout
Models, Molecular
Molecular and cellular biology
Molecular Sequence Data
Mutation
Mutation, Missense
Pedigree
Phenotype
Protein Structure, Tertiary
Receptor, Fibroblast Growth Factor, Type 3 - chemistry
Receptor, Fibroblast Growth Factor, Type 3 - deficiency
Receptor, Fibroblast Growth Factor, Type 3 - genetics
Sequence Homology, Amino Acid
Syndrome
Toes - abnormalities
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1086/508433