Compound heterozygous mutations of the TNXB gene cause primary myopathy

Pénisson-Besnier, I.; Allamand, Valérie; Beurrier, Philippe; Martin, Ludovic; Schalkwijk, Joost; Vlijmen-Willems, Ivonne van; Gartioux, C.; Malfait, Fransiska; Syx, Delfien; Macchi, Laurent; Marcorelles, Pascale; Arbeille, B.; Croué, Anne; Paepe, Anne De; Dubas, Frédéric

doi:10.1016/j.nmd.2013.04.009

Cited by 33 publications

(39 citation statements)

References 20 publications

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“…196 Tenascin-X is generally found in the connective tissue of cardiac, skeletal muscle, and skin, and its distribution is often distinct from that of tenascin-C. 197 Patients harboring mutations and deletions of tenascin-X exhibit phenotypic similarities with those who have Ehler-Danlos syndrome, including hyperelastic skin, increased joint and vascular laxity, and abnormal wound healing. [198][199][200][201] Tenascin-X is believed to modulate cellular adhesion and collagen stiffness. 202,203 Mice deficient in tenascin-X, like their human counterparts, exhibit skin hyperextensibility and fragility, with histologically normal-appearing collagen fibrils that are less densely packed.…”

Section: Figmentioning

confidence: 99%

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Chatterjee

Villarreal

Rhee

2014

Journal of Ocular Pharmacology and Therapeutics

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Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, and intraocular pressure (IOP) is an important modifiable risk factor. IOP is a function of aqueous humor production and aqueous humor outflow, and it is thought that prolonged IOP elevation leads to optic nerve damage over time. Within the trabecular meshwork (TM), the eye's primary drainage system for aqueous humor, matricellular proteins generally allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). It is now well established that ECM turnover in the TM affects outflow facility, and matricellular proteins are emerging as significant players in IOP regulation. The formalized study of matricellular proteins in TM has gained increased attention. Secreted protein acidic and rich in cysteine (SPARC), myocilin, connective tissue growth factor (CTGF), and thrombospondin-1 and -2 (TSP-1 and -2) have been localized to the TM, and a growing body of evidence suggests that these matricellular proteins play an important role in IOP regulation and possibly the pathophysiology of POAG. As evidence continues to emerge, these proteins are now seen as potential therapeutic targets. Further study is warranted to assess their utility in treating glaucoma in humans.

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Section: Figmentioning

confidence: 99%

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Chatterjee

Villarreal

Rhee

2014

Journal of Ocular Pharmacology and Therapeutics

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“…After the initial publication, additional cases have been reported, with a focus on specific clinical features, including neuromuscular, genito-urethral, gastrointestinal, and cardiovascular findings (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). So far, of 14 families only 18 patients with TNX-deficiency and two 2 with the contiguous gene syndrome have been reported, 14 of whom from the Netherlands.…”

mentioning

confidence: 99%

Recognizing the tenascin‐X deficient type of Ehlers–Danlos syndrome: a cross‐sectional study in 17 patients

et al. 2016

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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.

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“…Of the six major types of EDS, vascular type EDS patients are known to have the highest risk of gastrointestinal complications, namely, spontaneous and/or iatrogenic rupture of the sigmoid colon. 9 Upon review of the published work, we found that five of 19 patients of TNX-deficient type EDS (including this case) had gastrointestinal involvement (three hernias, 10,11 three diverticuloses, 10 two bowel perforations, 10 one recurrent rectal prolapse 10 and one gastrointestinal bleeding 12 ). Mutations in TNXB were identified in three of the five patients, and no apparent genotype-phenotype correlation was observed compared with other patients.…”

Section: Discussionmentioning

confidence: 81%

“…Mutations in TNXB were identified in three of the five patients, and no apparent genotype-phenotype correlation was observed compared with other patients. 11,12 The high incidence of gastrointestinal involvement in TNX-deficient type EDS patients indicates the importance of attention to invasive procedures and treatment of gastrointestinal disorders, not only in vascular type EDS but also in TNX-deficient type EDS.…”

Section: Discussionmentioning

confidence: 99%

Recurrent gastrointestinal perforation in a patient with Ehlers–Danlos syndrome due to tenascin‐X deficiency

Tomo

Kubo

Sasaki

et al. 2015

The Journal of Dermatology

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Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous disorder. Using a customized targeted exome-sequencing system we identified nonsense mutations in TNXB in a patient who had recurrent gastrointestinal perforation due to tissue fragility. This case highlights the utility of targeted exome sequencing for the diagnosis of congenital diseases showing genetic heterogeneity, and the importance of attention to gastrointestinal perforation in patients with tenascin-X deficient type EDS.

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Compound heterozygous mutations of the TNXB gene cause primary myopathy

Cited by 33 publications

References 20 publications

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Recognizing the tenascin‐X deficient type of Ehlers–Danlos syndrome: a cross‐sectional study in 17 patients

Recurrent gastrointestinal perforation in a patient with Ehlers–Danlos syndrome due to tenascin‐X deficiency

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