1. Department of Medical Genetics; Faculty of Medical Sciences; Tarbiat Modares University; 2. Department of Medical Genetics; Faculty of Medical Sciences; Tarbiat Modares University;
Abstract
Introduction
Myosin vi, encoded by myh6, is expressed dominantly in human cardiac atria and plays consequential roles in cardiac muscle contraction and comprising the cardiac muscle thick filament. mutations in the myh6 gene associated with atrial septal defect type 3 (asd3), hypertrophic (hcm) and dilated (dcm) cardiomyopathies. the novel mutation in this family, leads to a large spectrum of phenotypes including asd, thyroglossal sinus, refractive errors of the eye and meatal stenosis. the expansion of mutation spectrum of chd in the iranian population was fundamental goal of the present study.
Methods
Two patients in an iranian family have been identified who affected to congenital heart disease (chd). the first symptoms emerged at the birth and diagnosis based on clinical features was made at 5 years. the family had history of cardiomyopathy. for recognizing mutated gene(s), whole exome sequencing was performed for the patient and variants were analyzed by autosomal dominant inheritance model.
Results
Eventually by several filtering processes a c.3835c>t; r1279x mutation in myh6 gene (nm_002471.3) was identified as the most likely disease susceptibility variant and then confirmed by sanger sequencing in the family. this mutation results in elimination of the 660 amino acids in the c-terminal of myosin vi protein, including the vital parts of coiled coil structure of tail domain.
Conclusion
Our data indicates that c.3835c>t variant in myh6 gene is associated with cardiac malformations and provides a novel potential mechanism related to nonsense mutation.
