2.1. Sick sinus syndrome

At least one variation of the MYH6 gene has been associated with an increased risk of developing sick sinus syndrome. This condition affects the function of the sino-atrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The variation, which was identified in the Icelandic population, changes a single protein building block (amino acid) in the α-myosin heavy chain. Specifically, it replaces the amino acid arginine with the amino acid tryptophan at protein position 721 (written as Arg721Trp). Researchers found that about half of the people in their sample who had the Arg721Trp variation developed sick sinus syndrome during their lifetime, compared with about 6 percent of people who did not carry the variation. They speculated that the variation may alter the structure of the α-myosin heavy chain and disrupt its usual role in cardiac muscle contraction. These changes could alter the way the heart beats in some people, leading to an abnormally slow heartbeat (bradycardia) and related symptoms such as dizziness, light-headedness, and fainting (syncope).

2.2. Other disorders

Mutations in the MYH6 gene have been found to cause several additional heart conditions. These include congenital heart defects, particularly atrial-septal defect (ASD), which is a hole in the wall (septum) that separates the two upper chambers of the heart (the atria). Most of the MYH6 gene mutations associated with ASD affect a part of the α-myosin heavy chain known as the head domain. This part of the protein is involved in attaching (binding) type II myosin to actin. Abnormal interaction between these two proteins may disrupt early heart development, leading to heart defects such as ASD.

MYH6 gene mutations can also cause two diseases of the cardiac muscle, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). DCM weakens and enlarges the heart, while HCM is characterized by thickening (hypertrophy) of the cardiac muscle. Both of these conditions prevent the heart from pumping blood efficiently and increase the risk of heart failure and sudden death. Mutations associated with DCM and HCM can affect any part of the α-myosin heavy chain, and most change single amino acids in the protein. These changes likely alter the α-myosin heavy chain in ways that affect the structure and function of cardiac muscle.