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A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.

Giunta, C; Baumann, M; Fauth, C; Lindert, U; Abdalla, EM; Brady, AF; Collins, J; Dastgir, J; Donkervoort, S; Ghali, N; et al. Giunta, C; Baumann, M; Fauth, C; Lindert, U; Abdalla, EM; Brady, AF; Collins, J; Dastgir, J; Donkervoort, S; Ghali, N; Johnson, DS; Kariminejad, A; Koch, J; Kraenzlin, M; Lahiri, N; Lozic, B; Manzur, AY; Morton, JEV; Pilch, J; Pollitt, RC; Schreiber, G; Shannon, NL; Sobey, G; Vandersteen, A; van Dijk, FS; Witsch-Baumgartner, M; Zschocke, J; Pope, FM; Bönnemann, CG; Rohrbach, M (2018) A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history. Genet Med, 20 (1). pp. 42-54. ISSN 1530-0366 https://doi.org/10.1038/gim.2017.70
SGUL Authors: Lahiri, Nayana

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Abstract

PurposeIn 2012 we reported in six individuals a clinical condition almost indistinguishable from PLOD1-kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS), caused by biallelic mutations in FKBP14, and characterized by progressive kyphoscoliosis, myopathy, and hearing loss in addition to connective tissue abnormalities such as joint hypermobility and hyperelastic skin. FKBP14 is an ER-resident protein belonging to the family of FK506-binding peptidyl-prolyl cis-trans isomerases (PPIases); it catalyzes the folding of type III collagen and interacts with type III, type VI, and type X collagens. Only nine affected individuals have been reported to date.MethodsWe report on a cohort of 17 individuals with FKBP14-kEDS and the follow-up of three previously reported patients, and provide an extensive overview of the disorder and its natural history based on clinical, biochemical, and molecular genetics data.ResultsBased on the frequency of the clinical features of 23 patients from the present and previous cohorts, we define major and minor features of FKBP14-kEDS. We show that myopathy is confirmed by histology and muscle imaging only in some patients, and that hearing impairment is predominantly sensorineural and may not be present in all individuals.ConclusionOur data further support the extensive clinical overlap with PLOD1-kEDS and show that vascular complications are rare manifestations of FKBP14-kEDS.

Item Type: Article
Additional Information: This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ © The Author(s) 2018
Keywords: Genetics & Heredity, 0604 Genetics, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Journal or Publication Title: Genet Med
ISSN: 1530-0366
Language: eng
Dates:
DateEvent
January 2018Published
15 June 2017Published Online
5 April 2017Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-Share Alike 4.0
Projects:
Project IDFunderFunder ID
310030_138288Swiss National Science Foundationhttp://dx.doi.org/10.13039/501100001711
PubMed ID: 28617417
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109734
Publisher's version: https://doi.org/10.1038/gim.2017.70

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