PUBLICATION
Identification of a novel insertion mutation in FGFR3 that causes thanatophoric dysplasia type 1
- Authors
- Lindy, A.S., Basehore, M.J., Munisha, M., Williams, A.L., Friez, M.J., Writzl, K., Willems, P., Dougan, S.T.
- ID
- ZDB-PUB-160401-15
- Date
- 2016
- Source
- American journal of medical genetics. Part A 170(6): 1573-9 (Journal)
- Registered Authors
- Dougan, Scott T., Williams, Aimee
- Keywords
- fibroblast growth factor receptor, insertion mutation, neonatal dwarfism, prenatal diagnosis, thanatophoric dysplasia, zebrafish
- MeSH Terms
-
- Abortion, Induced
- Alleles
- Animals
- Autopsy
- Exons
- Female
- Fetus
- Gene Expression
- Genetic Association Studies*
- Genotype
- Humans
- Mutagenesis, Insertional*
- Mutation
- Phenotype*
- Pregnancy
- Receptor, Fibroblast Growth Factor, Type 3/deficiency*
- Receptor, Fibroblast Growth Factor, Type 3/genetics*
- Thanatophoric Dysplasia/diagnosis*
- Thanatophoric Dysplasia/genetics*
- Zebrafish
- PubMed
- 27028100 Full text @ Am. J. Med. Genet. A
Citation
Lindy, A.S., Basehore, M.J., Munisha, M., Williams, A.L., Friez, M.J., Writzl, K., Willems, P., Dougan, S.T. (2016) Identification of a novel insertion mutation in FGFR3 that causes thanatophoric dysplasia type 1. American journal of medical genetics. Part A. 170(6):1573-9.
Abstract
Thanatophoric dysplasia is a type of short-limbed neonatal dwarfism that is usually lethal in the perinatal period. It is characterized by short limbs, a narrow, bell-shaped thorax, macrocephaly with a prominent forehead, and flattened vertebral bodies. These malformations result from autosomal dominant mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. In this report, we describe a novel FGFR3 insertion mutation in a fetus with shortened limbs, curved femurs, and a narrow thorax. The diagnosis of thanatophoric dysplasia type 1 was suspected clinically, and FGFR3 sequencing showed a c.742_743insTGT variant, which predicts p.R248delinsLC. In vivo studies in zebrafish demonstrated that this mutation resulted in the overexpression of zebrafish Fgfr3, leading to the over-activation of downstream signaling and dorsalized embryos. To date, no insertions or deletions in FGFR3 have been reported to cause thanatophoric dysplasia types 1 or 2; therefore, this represents the first report to describe such a mutation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping