Recognizing the tenascin‐X deficient type of Ehlers–Danlos syndrome: a cross‐sectional study in 17 patients
Open accessAbstract
The tenascin‐X (TNX) deficient type Ehlers–Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX‐deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross‐sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next‐generation sequencing (NGS), Sanger sequencing and multiplex ligation‐dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non‐sense mRNA mediated decay. In short, patients with the TNX‐deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency
Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., & Bristow, J. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa002939 · Cited by 391 · see citing works
Self-citationTenascin-X deficiency is associated with Ehlers-Danlos syndrome
Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., Miller, W. L., & Bristow, J. (1997) · Nature Genetics · doi:10.1038/ng0997-104 · Cited by 366 · see citing works
Postural tachycardia syndrome—current experience and concepts
Mathias, C. J., Low, D. A., Iodice, V., Owens, A. P., Kirbis, M., & Grahame, R. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.187 · Cited by 251 · cited 1× · see citing works
“Peripheral blood pooling as part of postural tachycardia syndrome or venous insufficiency related to subcutaneous tissue laxity might play a role (20).”
BackgroundHaploinsufficiency of TNXB Is Associated with Hypermobility Type of Ehlers-Danlos Syndrome
Zweers, M. C., Bristow, J., Steijlen, P. M., Dean, W. B., Hamel, B. C., Otero, M., Kucharekova, M., Boezeman, J. B., & Schalkwijk, J. (2003) · The American Journal of Human Genetics · doi:10.1086/376564 · Cited by 242 · see citing works
Self-citationPain in Ehlers-Danlos Syndrome Is Common, Severe, and Associated with Functional Impairment
Voermans, N. C., Knoop, H., Bleijenberg, G., & van Engelen, B. G. (2010) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2009.12.026 · Cited by 237 · see citing works
Self-citationMerke, D. P., Chen, W., Morissette, R., Xu, Z., Van Ryzin, C., Sachdev, V., Hannoush, H., Shanbhag, S. M., Acevedo, A. T., Nishitani, M., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3148 · Cited by 82 · see citing works
Reduced quantitative muscle function in tenascin-X deficient Ehlers-Danlos patients
Voermans, N. C., Altenburg, T. M., Hamel, B. C., de Haan, A., & van Engelen, B. G. (2007) · Neuromuscular Disorders · doi:10.1016/j.nmd.2007.04.004 · Cited by 36 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Ehlers–Danlos syndromes, rare types
Brady, A. F., Demirdas, S., Fournel‐Gigleux, S., Ghali, N., Giunta, C., Kapferer‐Seebacher, I., Kosho, T., Mendoza‐Londono, R., Pope, M. F., Rohrbach, M., et al. (2017) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31550 · Cited by 249 · see citing works
Self-citationVascular aspects of the Ehlers-Danlos Syndromes
Malfait, F. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.04.013 · Cited by 113 · see citing works
Tenascin-X, Congenital Adrenal Hyperplasia, and the CAH-X Syndrome
Miller, W. L., & Merke, D. P. (2018) · Hormone Research in Paediatrics · doi:10.1159/000481911 · Cited by 61 · see citing works
Gao, Y., Lu, L., Yu, B., Mao, J., Wang, X., Nie, M., & Wu, X. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa199 · Cited by 31 · see citing works
Lao, Q., Brookner, B., & Merke, D. P. (2019) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2019.06.001 · Cited by 29 · see citing works
Tenascin-X—Discovery and Early Research
Miller, W. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.612497 · Cited by 26 · see citing works
A novel role for the extracellular matrix glycoprotein‐Tenascin‐X in gastric function
Aktar, R., Peiris, M., Fikree, A., Eaton, S., Kritas, S., Kentish, S. J., Araujo, E. J. A., Bacarin, C., Page, A. J., Voermans, N. C., et al. (2019) · The Journal of Physiology · doi:10.1113/jp277195 · Cited by 25 · see citing works
Self-citationScicluna, K., Formosa, M. M., Farrugia, R., & Borg, I. (2022) · Clinical Genetics · doi:10.1111/cge.14026 · Cited by 20 · see citing works
Fanis, P., Skordis, N., Phylactou, L. A., & Neocleous, V. (2023) · HORMONES · doi:10.1007/s42000-022-00410-w · Cited by 4 · see citing works
“More specifically, our case has normal skin when compared to certain patients with biallelic CAH-X genotype and who typically demonstrate skin laxity and abnormal wound healing [45, 46].”
Result
- Authors
- Demirdas, S., Dulfer, E., Robert, L., Kempers, M., van Beek, D., Micha, D., van Engelen, B. G., Hamel, B., Schalkwijk, J., Loeys, B., Maugeri, A., & Voermans, N. C.
- Affiliations
- Radboud University Nijmegen (NL)
- University Medical Center Groningen (NL)
- Guy's Hospital (GB)
- Department of Clinical Genetics, Centre for Connective Tissue Research VU University Medical Centre Amsterdam the Netherlands
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Department of Dermatology Radboud University Medical Centre Nijmegen the Netherlands
- Corresponding author
- Voermans, N.C.
- ORCID
- Venue
- Clinical Genetics
- Publisher
- Wiley
- Published
- 2016-11-04
- Volume
- 91
- Issue
- 3
- Pages
- 411-425
- ISSN
- 0009-9163 (ISSN-L)
- 1399-0004
- OpenAlex
- W2516645790
- Cited by
- 60
- References
- 7
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 7 · 2019: 9 · 2018: 4 · 2017: 4
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Clinical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Radboud Universitair Medisch Centrum
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Keywords
- Ehlers-Danlos syndrome, tenascin-X, autosomal recessive inheritance, joint hypermobility, skin hyperextensibility, easy bruising, atrophic scars, genetic diagnosis, nonsense mutation, underdiagnosis
- MeSH terms
- Adolescent, Adult, Aged, Child, Cross-Sectional Studies, Diagnosis, Differential, Ehlers-Danlos Syndrome, Female, Humans, Joint Instability, Male, Middle Aged, Mutation, Skin Abnormalities, Tenascin, Young Adult, High-Throughput Nucleotide Sequencing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
