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Functional missense and splicing variants in the retinoic acid catabolizing enzyme CYP26C1 in idiopathic short stature

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 phenotyp...

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Bibliographische Detailangaben
Hauptverfasser: Montalbano, Antonino (VerfasserIn) , Jürgensen, Lonny (VerfasserIn) , Röth, Ralph (VerfasserIn) , Weiß, Birgit (VerfasserIn) , Hassel, David (VerfasserIn) , Rappold, Gudrun (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 30 April 2018
In: European journal of human genetics
Year: 2018, Jahrgang: 26, Heft: 8, Pages: 1113-1120
ISSN:1476-5438
DOI:10.1038/s41431-018-0148-9
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41431-018-0148-9
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41431-018-0148-9
Volltext
Verfasserangaben:Antonino Montalbano, Lonny Juergensen, Maki Fukami, Christian T. Thiel, Nadine H. Hauer, Ralph Roeth, Birgit Weiss, Yasuhiro Naiki, Tsutomu Ogata, David Hassel, Gudrun A. Rappold
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 16.04.2020
Beschreibung:Online Resource
ISSN:1476-5438
DOI:10.1038/s41431-018-0148-9

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