Characterization of the first FGFRL1 mutation identified in a craniosynostosis patient

Rieckmann, Thorsten; Zhuang, Lei; Flück, Christa E; Trueb, Beat (2009). Characterization of the first FGFRL1 mutation identified in a craniosynostosis patient. Biochimica et biophysica acta - molecular basis of disease, 1792(2), pp. 112-21. New York, N.Y.: Elsevier 10.1016/j.bbadis.2008.11.006

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Fibroblast growth factor receptor-like 1 (FGFRL1) is a recently discovered transmembrane protein whose functions remain unclear. Since mutations in the related receptors FGFR1-3 cause skeletal malformations, DNA samples from 55 patients suffering from congenital skeletal malformations and 109 controls were searched for mutations in FGFRL1. One patient was identified harboring a frameshift mutation in the intracellular domain of this novel receptor. The patient showed craniosynostosis, radio-ulnar synostosis and genital abnormalities and had previously been diagnosed with Antley-Bixler syndrome. The effect of the FGFRL1 mutation was studied in vitro. In a reporter gene assay, the wild-type as well as the mutant receptor inhibited FGF signaling. However, the mutant protein differed from the wild-type protein in its subcellular localization. Mutant FGFRL1 was mainly found at the plasma membrane where it interacted with FGF ligands, while the wild-type protein was preferentially located in vesicular structures and the Golgi complex. Two motifs from the intracellular domain of FGFRL1 appeared to be responsible for this differential distribution, a tandem tyrosine based motif and a histidine-rich sequence. Deletion of either one led to the preferential redistribution of FGFRL1 to the plasma membrane. It is therefore likely that mutant FGFRL1 contributes to the skeletal malformations of the patient.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Rieckmann, Thorsten; Zhuang, Lei; Flück, Christa and Trueb, Beat

ISSN:

0925-4439

ISBN:

19056490

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:03

Last Modified:

04 May 2014 23:19

Publisher DOI:

10.1016/j.bbadis.2008.11.006

PubMed ID:

19056490

Web of Science ID:

000263430800004

URI:

https://boris.unibe.ch/id/eprint/27187 (FactScience: 104908)

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