Homozygous missense MYBPC3 Pro873His mutation associated with increased risk for heart failure development in hypertrophic cardiomyopathy
| Autor: | Cecilia Gunnarsson, Anna Gréen, Jon Jonasson, Cecilia Trinks, Jan-Erik Karlsson, Antheia Kissopoulou |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Heart transplantation medicine.medical_specialty business.industry medicine.medical_treatment Hypertrophic cardiomyopathy macromolecular substances 030204 cardiovascular system & hematology medicine.disease Penetrance 3. Good health 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Internal medicine Heart failure medicine Cardiology Medical genetics Missense mutation cardiovascular diseases Allele Cardiology and Cardiovascular Medicine business Genotyping |
| Zdroj: | ESC Heart Failure. 5:716-723 |
| ISSN: | 2055-5822 |
| DOI: | 10.1002/ehf2.12288 |
| Popis: | Hypertrophic cardiomyopathy (HCM) is a primary autosomal-dominant disorder of the myocardium with variable expressivity and penetrance. Occasionally, homozygous sarcomere genetic variants emerge while genotyping HCM patients. In these cases, a more severe HCM phenotype is generally seen. Here, we report a case of HCM that was diagnosed clinically at 39 years of age. Initial symptoms were shortness of breath during exertion. Successively, he developed a wide array of severe clinical manifestations, which progressed to an ominous end-stage heart failure that resulted in heart transplantation. Genotype analysis revealed a missense MYBPC3 variant NM_000256.3:c.2618C>A,p.(Pro873His) that presented in the homozygous form. Conflicting interpretations of pathogenicity have been reported for the Pro873His MYBPC3 variant described here. Our patient, presenting with two copies of the variant and devoid of a normal allele, progressed to end-stage heart failure, which supports the notion of a deleterious effect of this variant in the homozygous form. |
| Databáze: | OpenAIRE |
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