A high risk phenotype of hypertrophic cardiomyopathy associated with a compound genotype of two mutated beta-myosin heavy chain genes

Human Genetics
B JeschkeH P Vosberg

Abstract

Hypertrophic cardiomyopathy (HCM) is a genetically and clinically heterogeneous myocardial disease that is in most cases familial and transmitted in a dominant fashion. The most frequently affected gene codes for the cardiac (ventricular) beta-myosin heavy chain. We have investigated the genetic cause of an isolated case of HCM, which was marked by an extremely severe phenotype and a very early age of onset. HCM is normally not a disease of small children. The proband was a boy who had suffered cardiac arrest at the age of 6.5 years (resuscitation by cardioconversion). Upon screening of the beta-myosin heavy chain gene as a candidate, two missense mutations, one in exon 19 (Arg719Trp) and a second in exon 12 (Met349Thr), were identified. The Arg719Trp mutation was de novo, as it was not found in the parents. In contrast, the Met349Thr mutation was inherited through the maternal grandmother. Six family members were carriers of this mutation but only the proband was clinically affected. Segregation and molecular analysis allowed us to assign the Met349Thr mutation to the maternal and the Arg719Trp de novo mutation to the paternal beta-myosin allele. Thus, the patient has no normal myosin. We interpret these findings in terms of c...Continue Reading

Citations

Jun 7, 2000·Journal of the American College of Cardiology·S T LiD S Goldstein
Mar 26, 2003·Journal of the American College of Cardiology·Ali J Marian
May 5, 2000·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·G Shah, R Roberts
May 17, 2002·Current Opinion in Cardiology·A J Marian
Sep 3, 2008·Clinical and Experimental Pharmacology & Physiology·Tatiana TsoutsmanChristopher Semsarian
Nov 21, 2001·Current Controlled Trials in Cardiovascular Medicine·Hans-Peter Vosberg
Mar 29, 2001·Journal of Molecular and Cellular Cardiology·A J Marian, R Roberts
Jan 31, 2015·Cardiovascular Research·Carolyn Y HoYigal Pinto
Jun 4, 2008·Circulation·Lisa Dellefave, Elizabeth M McNally
Dec 25, 2009·Circulation. Cardiovascular Genetics·Matthew Kelly, Christopher Semsarian
Dec 25, 2009·Circulation. Cardiovascular Genetics·Juan Pablo KaskiPerry M Elliott
Nov 6, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Norman R AlpertLameh Fananapazir
May 22, 1998·Medizinische Klinik·H P Vosberg
Mar 2, 2005·Biochemical and Biophysical Research Communications·Ping WangRutai Hui

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.