(CARDIoG): "Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects"
Study Details
Study Description
Brief Summary
The objective of the study is to investigate congenital disorders of glycosylation in congenital heart diseases without a clear molecular or genetic basis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Congenital disorders of glycosylation (CDG) are a family of inherited disorders caused by defects in the synthesis of glycans, glycoproteins or other glycoconjugates. Congenital disorders of glycosylation (CDG) are a family of inherited disorders caused by defects in the synthesis of glycans, glycoproteins or other glycoconjugates. Glycosylation of proteins is crucial for a proper organ morphogenesis and for an appropriate coagulation system functioning. The neurological system is commonly affected in this type of disorders but cases of CDG with normal neurological development have been recently described. The group of Experimental Hematology and Clinic Oncology of the University of Murcia (Spain) recently described a rare disorder of glycosylation (ALG12-CDG) as the cause of antithrombin deficiency in a patient of 19 years with a history of repaired ventricular septal defect.
On the other hand, population studies have shown an increased incidence of thromboembolic events in patients with congenital heart disease when compared to the general population. The identified genetic defects involved in the development of congenital heart diseases have variable or incomplete penetrance and in most cases the molecular basis is completely unknown.
The investigators postulate that a CDG might be behind the development of some forms of congenital heart disease and contribute to the greater prevalence of thromboembolic events in this patient population.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| patients with congenital heart disease patients with congenital heart disease |
Other: none intervention
|
Outcome Measures
Primary Outcome Measures
- Disorders of glycosylation [1 year]
Secondary Outcome Measures
- Incidence of antithrombin deficiency [1 year]
Other Outcome Measures
- Genetical alteractions of disorders of glycosylation [1 year]
- Association between disorders of glycosylation and thromboembolic events [1 year]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Adult with a congenital heart disease with most probability to present a congenital disorder of glycosylation of proteins
Exclusion Criteria:
- Denial of informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vall d'Hebron Hospital | Barcelona | Spain | 08035 |
Sponsors and Collaborators
- Hospital Universitari Vall d'Hebron Research Institute
- Universidad de Murcia
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Aguila S, Martínez-Martínez I, Dichiara G, Gutiérrez-Gallego R, Navarro-Fernández J, Vicente V, Corral J. Increased N-glycosylation efficiency by generation of an aromatic sequon on N135 of antithrombin. PLoS One. 2014 Dec 8;9(12):e114454. doi: 10.1371/journal.pone.0114454. eCollection 2014. Erratum in: PLoS One. 2015;10(3):e0122177.
- de la Morena-Barrio ME, Hernández-Caselles T, Corral J, García-López R, Martínez-Martínez I, Pérez-Dueñas B, Altisent C, Sevivas T, Kristensen SR, Guillén-Navarro E, Miñano A, Vicente V, Jaeken J, Lozano ML. GPI-anchor and GPI-anchored protein expression in PMM2-CDG patients. Orphanet J Rare Dis. 2013 Oct 20;8:170. doi: 10.1186/1750-1172-8-170.
- Dorn C, Grunert M, Sperling SR. Application of high-throughput sequencing for studying genomic variations in congenital heart disease. Brief Funct Genomics. 2014 Jan;13(1):51-65. doi: 10.1093/bfgp/elt040. Epub 2013 Oct 3. Review.
- Footitt EJ, Karimova A, Burch M, Yayeh T, Dupré T, Vuillaumier-Barrot S, Chantret I, Moore SE, Seta N, Grunewald S. Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review. J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S313-9. doi: 10.1007/s10545-009-1262-1. Epub 2009 Sep 7. Review.
- Gehrmann J, Sohlbach K, Linnebank M, Böhles HJ, Buderus S, Kehl HG, Vogt J, Harms E, Marquardt T. Cardiomyopathy in congenital disorders of glycosylation. Cardiol Young. 2003 Aug;13(4):345-51. Review.
- Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014 Mar 21;14:38. doi: 10.1186/1471-2261-14-38.
- Martínez-Martínez I, Ordóñez A, Navarro-Fernández J, Pérez-Lara A, Gutiérrez-Gallego R, Giraldo R, Martínez C, Llop E, Vicente V, Corral J. Antithrombin Murcia (K241E) causing antithrombin deficiency: a possible role for altered glycosylation. Haematologica. 2010 Aug;95(8):1358-65. doi: 10.3324/haematol.2009.015487. Epub 2010 Apr 30.
- Mitra N, Sinha S, Ramya TN, Surolia A. N-linked oligosaccharides as outfitters for glycoprotein folding, form and function. Trends Biochem Sci. 2006 Mar;31(3):156-63. Epub 2006 Feb 10. Review. Erratum in: Trends Biochem Sci. 2006 May;31(5):251.
- Romano S, Bajolle F, Valayannopoulos V, Lyonnet S, Colomb V, de Baracé C, Vouhe P, Pouard P, Vuillaumier-Barrot S, Dupré T, de Keyzer Y, Sidi D, Seta N, Bonnet D, de Lonlay P. Conotruncal heart defects in three patients with congenital disorder of glycosylation type Ia (CDG Ia). J Med Genet. 2009 Apr;46(4):287-8. doi: 10.1136/jmg.2008.057620.
- CARDIoG