PUBLICATION
Functional missense and splicing variants in the retinoic acid catabolizing enzyme CYP26C1 in idiopathic short stature
- Authors
- Montalbano, A., Juergensen, L., Fukami, M., Thiel, C.T., Hauer, N.H., Roeth, R., Weiss, B., Naiki, Y., Ogata, T., Hassel, D., Rappold, G.A.
- ID
- ZDB-PUB-180502-3
- Date
- 2018
- Source
- European journal of human genetics : EJHG 26(8): 1113-1120 (Journal)
- Registered Authors
- Hassel, David
- Keywords
- none
- MeSH Terms
-
- Adolescent
- Adult
- Animals
- Cell Line, Tumor
- Child
- Cytochrome P450 Family 26/genetics*
- Cytochrome P450 Family 26/metabolism
- Dwarfism, Pituitary/genetics*
- Dwarfism, Pituitary/pathology
- Exome
- Female
- Humans
- Male
- Mutation, Missense*
- RNA Splicing
- Zebrafish
- PubMed
- 29706635 Full text @ Eur. J. Hum. Genet.
Citation
Montalbano, A., Juergensen, L., Fukami, M., Thiel, C.T., Hauer, N.H., Roeth, R., Weiss, B., Naiki, Y., Ogata, T., Hassel, D., Rappold, G.A. (2018) Functional missense and splicing variants in the retinoic acid catabolizing enzyme CYP26C1 in idiopathic short stature. European journal of human genetics : EJHG. 26(8):1113-1120.
Abstract
Height is a complex quantitative trait with a high heritability. Short stature is diagnosed when height is significantly below the average of the general population for that person's age and sex. We have recently found that the retinoic acid degrading enzyme CYP26C1 modifies SHOX deficiency phenotypes toward more severe clinical manifestations. Here, we asked whether damaging variants in CYP26C1 alone could lead to short stature. We performed exome and Sanger sequencing to analyze 856 individuals with short stature where SHOX deficiency was previously excluded. Three different damaging missense variants and one splicing variant were identified in six independent individuals; the functional significance of the identified variants was tested in vitro or in vivo using zebrafish as a model. The genetic and functional data reported here indicate that CYP26C1 represents a novel gene underlying growth disorders and that damaging variants in the absence of SHOX variants can lead to short stature.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping