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Researchers Link Gene Mutations to Ebstein’s Anomaly

Ebstein’s anomaly is a rare congenital valvular heart disease. Now, in patients with this disease, researchers of the Academic Medical Center Amsterdam in the Netherlands, the University of Newcastle, UK and the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have identified mutations in a gene which plays an important role in the structure of the heart. The researchers hope that these findings will lead to faster diagnosis and novel, more specifically targeted treatment methods (Circulation Cardiovascular Genetics, DOI: 10.1161/CIRCGENETICS.110.957985)*.

anomaly is a heart defect in which the valve between the right ventricle and
the right atrium is abnormally formed. Since the heart valve cannot close
properly, heart function is compromised. Some patients with Ebstein’s
anomaly additionally suffer from a myocardial disease called left ventricular noncompaction (LVNC). This disease is associated with
increased risk for sudden cardiac death or inadequate functioning of the heart
muscle (myocardial insufficiency).

A few
years ago in a study of LVNC patients, Prof. Ludwig Thierfelder and Dr. Sabine Klaassen (both MDC) discovered mutations in three different
genes that encode muscle structural proteins. These proteins are important for
heart contraction and for enabling the blood to be pumped through the body. One
gene in which the MDC researchers identified mutations is the gene MYH7. Mutations in this gene in LVNC
patients cause sponge-like muscle tissue to protrude into the left ventricle,
thus impairing the contractile performance of the heart.

As a
consequence of these findings, Dr. Alex V. Postma
from Amsterdam, Professor Judith Goodship from
Newcastle and PD Dr. Klaassen from the MDC sought to
determine whether an association exists between Ebstein’s
anomaly, LVNC and mutations in the gene MYH7.
In a multicenter study of cohorts from the Netherlands, Germany and the UK,
they studied 141 Ebstein’s patients who were not
related to each other for mutations in MYH7. In eight of the study participants, the
researchers identified mutations in this gene. Six of these patients also suffered
from the myocardial disease LVNC in addition to Ebstein’s

these results we conclude that one mutation can lead to different congenital
heart diseases. These can even occur concurrently, as here with Ebstein’s anomaly and LVNC,” said Dr. Klaassen.
“In these cases we recommend that other family members also undergo cardiac
examinations and genetic testing, since the risk for heart arrhythmia or heart
failure is increased in mutation carriers even if they are not known to have a
congenital heart defect. The earlier the mutations encoding the structural
proteins of the heart are recognized, the better: close monitoring, long-term
ECG recording and drug treatment can be conducted at an early stage. This means
that physicians can advise and treat their patients more effectively.”

*Mutations in the Sarcomere Gene MYH7 in Ebstein’s Anomaly

Alex V. Postma, PhD 1 ,Klaartje van Engelen, MD 2,3 ,Judith van de Meerakker, MSc 1 Thahira Rahman, PhD 4 ,Susanne Probst, PhD 5 ,Marieke J.H. Baars, MD 3  ,Ulrike Bauer, MD 6 ,Thomas Pickardt, PhD 6   ,Silke R. Sperling, MD 7  ,Felix Berger, MD 8  ,Antoon F.M. Moorman, MD, PhD1  ,Barbara J.M. Mulder, MD, PhD 2  ,Ludwig Thierfelder, MD 5  ,Bernard Keavney, MD 4  ,Judith Goodship, MD 4  ,Sabine Klaassen, MD 5,8

1Heart Failure Research Center, Department of Anatomy, Embryology and Physiology, Academic Medical Center, Amsterdam, The Netherlands

2Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands;

3Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands;

4Institute of Human Genetics, Newcastle University, Newcastle,

5Max-Delbrück-Center for Molecular Medicine, Berlin, Germany;

6National Registry for Congenital Heart Defects, Berlin, Germany;

7Max Planck Institute for Molecular Genetics, Berlin, Germany;

8Department of Congenital Heart Defects/Pediatric Cardiology, German Heart Institute Berlin and Charité, University Medicine Berlin, Germany on behalf of “Heart Repair Line 1”, EU 6th Framework Program, CONCOR (National Registry and DNA bank of congenital heart defects Netherlands), and Competence Network for Congenital Heart Defects, Germany

Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10
13125 Berlin
Phone: +49 (0) 30 94 06 - 38 96
Fax:     +49 (0) 30 94 06 - 38 33

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