Lack of evidence for a causal role of CALR3 in monogenic cardiomyopathy
| Autor: | Ronald H. Lekanne Deprez, Jan D. H. Jongbloed, Job H. Veldman, Paul A. van der Zwaag, Marja W. Wessels, Jan H. von der Thüsen, Ingrid M.B.H. van de Laar, Dennis Dooijes, Marjon van Slegtenhorst, Jasper J. van der Smagt, Arthur van den Wijngaard, Erwin Brosens, Michelle Michels, Anneke M. van Mil, Robert M.W. Hofstra, Rogier A. Oldenburg, Imke Christiaans, Apollonia T. J. M. Helderman-van den Enden, Judith M.A. Verhagen |
|---|---|
| Přispěvatelé: | Cardiovascular Centre (CVC), MUMC+: DA KG Lab Centraal Lab (9), RS: FHML non-thematic output, Human Genetics, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, Clinical Genetics, Pathology, Cardiology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proband Adult Male Heterozygote Population Cardiomyopathy Mutation Missense PROTEIN ESC Disease DIAGNOSTICS GUIDELINES Article 03 medical and health sciences GENETIC-VARIANTS Genetics medicine Missense mutation Humans education Gene Genetics (clinical) education.field_of_study Polymorphism Genetic HYPERTROPHIC CARDIOMYOPATHY business.industry Myocardium Hypertrophic cardiomyopathy Middle Aged medicine.disease Pedigree 030104 developmental biology CALRETICULIN Cohort Female business Cardiomyopathies PATHOGENICITY |
| Zdroj: | European Journal of Human Genetics, 26(11), 1603-1610. Nature Publishing Group European Journal of Human Genetics European journal of human genetics, 26(11), 1603-1610. Nature Publishing Group |
| ISSN: | 1018-4813 |
| Popis: | The pathogenicity of previously published disease-associated genes and variants is sometimes questionable. Large-scale, population-based sequencing studies have uncovered numerous false assignments of pathogenicity. Misinterpretation of sequence variants may have serious implications for the patients and families involved, as genetic test results are increasingly being used in medical decision making In this study, we assessed the role of the calreticulin-3 gene (CALR3) in cardiomyopathy. CALR3 has been included in several cardiomyopathy gene panels worldwide. Its inclusion is based on a single publication describing two missense variants in patients with hypertrophic cardiomyopathy. In our national cardiomyopathy cohort (n = 6154), we identified 17 unique, rare heterozygous CALR3 variants in 48 probands. Overall, our patient cohort contained a significantly higher number of rare CALR3 variants compared to the ExAC population (p = 0.0036). However, after removing a potential Dutch founder variant, no statistically significant difference was found (p = 0.89). In nine probands, the CALR3 variant was accompanied by a disease-causing variant in another, well-known cardiomyopathy gene. In three families, the CALR3 variant did not segregate with the disease. Furthermore, we could not demonstrate calreticulin-3 protein expression in myocardial tissues at various ages. On the basis of these findings, it seems highly questionable that variants in CALR3 are a monogenic cause of cardiomyopathy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink