Ehlers-Danlos Treatment Report

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gene therapy

Genetic Variations in Patients with Ehlers-Danlos Syndrome

https://clinicaltrials.gov/ct2/show/NCT03093493

Genetics of Ehlers-Danlos Syndrome

Study Type : Observational [Patient Registry] Estimated Enrollment : 300 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 1 Year
Official Title: Determine the Causative Genetic Variations in Patients With Ehlers-Danlos Syndrome
Actual Study Start Date : August 25, 2017
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Ehlers-Danlos Syndrome-Related Genes and Serum Strontium, Zinc, and Lithium Levels in Generalized Joint Hypermobility

https://www.tandfonline.com/doi/abs/10.1080/03008207.2019.1675648?journalCode=icts20

https://pubmed.ncbi.nlm.nih.gov/31594391-ehlers-danlos-syndrome-related-genes-and-serum-strontium-zinc-and-lithium-levels-in-generalized-joint-hypermobility-a-case-control-study/

Ehlers-Danlos Syndrome-Related Genes and Serum Strontium, Zinc, and Lithium Levels in Generalized Joint Hypermobility: A Case-Control Study

Abstract

Aim of the study: Generalized joint hypermobility (GJH) is a common feature of almost all Ehlers-Danlos syndrome (EDS) types; however, its genetic basis remains unclear. Therefore, it is crucial to distinguish the genetic basis of GJH from other connective tissue disorders, including the different subtypes of EDS. The aim of this study was to determine the blood EDS-related gene expressions and serum element levels in GJH and reveal their predictive characteristics and correlations with the Beighton score. Materials and Methods: A total of 39 women aged 18-23 years with GJH and 38 age- and sex-matched controls were included in the study. Inductively coupled plasma mass spectrometry was used to analyze the serum levels of zinc (Zn), strontium (Sr), and lithium (Li). The relative expression levels of the EDS-related genes were determined using quantitative real-time polymerase chain reaction (PCR). Results: Our results showed that women with GJH possessed significantly lower Li and higher Zn and Sr levels than the controls. In addition, the gene expressions of TNXB and SLC39A13 were significantly higher, whereas those of COL1A1, COL1A2, COL5A1, FKBP14, and DSE were lower in the GJH group. Pearson correlation analyses revealed a strong negative correlation between the Beighton score and B4GALT7, FKBP14, COL1A1, and Li. However, a significant positive correlation was noted between the Beighton score and SLC39A13, TNXB, Zn, Sr, and B3GALT6. Conclusion: Our findings provide valuable basal levels for conducting gene function analysis of joint hypermobility-related connective tissue disorders.

A Novel Frameshift COL3A1 Variant in Vascular Ehlers-Danlos Syndrome: insight into genetic variants and clinical expression of vEDS

https://www.annalsofvascularsurgery.com/article/S0890-5096(19)30553-9/fulltext

https://www.sciencedirect.com/science/article/abs/pii/S0890509619305539

https://www.ncbi.nlm.nih.gov/pubmed/31394236?dopt=Abstract

A Novel Frameshift COL3A1 Variant in Vascular Ehlers-Danlos Syndrome

Ehlers-Danlos syndromes (EDSs) are a group of heritable connective tissue disorders with distinct genetic etiologies. Of the 13 currently recognized types of EDS, the vascular type EDS (vEDS) is generally considered the most severe and is associated with a decreased life expectancy due to spontaneous arterial, intestinal, and or uterine rupture. Diagnosis of vEDS is supported by genetic testing confirming the presence of pathogenic variations in COL3A1, a type III procollagen gene. Management of vEDS is usually conservative with control of hemodynamic stress, frequent cardiovascular imaging, and, if indicated, a thoughtful endovascular intervention or surgical repair. We present a novel frameshift variant in COL3A1 leading to vEDS with multiple vascular involvements. Based on our literature review, this variant has not been reported and may result in a less severe form of vEDS. Our case report provides insight into genetic variants and clinical expression of vEDS.

Genetic basis of hereditary thoracic aortic aneurysms and dissections, including vascular Ehlers-Danlos syndrome

https://www.journal-of-cardiology.com/article/S0914-5087(19)30086-3/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/31000321?dopt=Abstract

Related Articles

Genetic basis of hereditary thoracic aortic aneurysms and dissections.

J Cardiol. 2019 Apr 15;:

Authors: Takeda N, Komuro I

Abstract

Recent advances in DNA sequencing technology have identified several causative genes for hereditary thoracic aortic aneurysms and dissections (TAADs), including Marfan syndrome (MFS), Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and familial non-syndromic TAADs. Syndromic TAADs are typically caused by pathogenic variants in the transforming growth factor-β signal and extracellular matrix-related genes (e.g. FBN1, TGFBR1, TGFBR2, SMAD3, TGFB2, and COL3A1). On the other hand, approximately 20% of the non-syndromic hereditary TAADs result from altered components of the contractile apparatus of vascular smooth muscle cells, which are encoded by ACTA2, MYH11, MYLK, and PRKG1 genes; however, the remaining 80% cannot be explained by previously reported candidate genes. Moreover, the relationship between the genotype and phenotype of TAADs has extensively been reported to investigate better methods for risk stratification and further personalized treatment strategies. With regard to MFS-causing FBN1, recent reports have shown significantly increased risk of aortic events in patients carrying a truncating variant or a variant exhibiting a haploinsufficient-type effect, typically comprising nonsense or small insertions/deletions resulting in out-of-frame effects, compared to those carrying a variant with dominant negative-type effect, typically comprising missense variants. Therefore, cardiologists are required to have sufficient knowledge regarding the genetics of hereditary TAADs for providing the best clinical management, with an appropriate genetic counseling. In the current review, we present current advances in the genetics of hereditary TAADs and discuss the benefits and limitations with respect to the use of this genetic understanding in clinical settings.

PMID: 31000321 [PubMed – as supplied by publisher]

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