Electrical storm (ES) is a life threatening clinical situation. Though a few clinical pointers exist, the occurrence of ES in a patient with remote myocardial infarction (MI) is generally unpredictable. Genetic markers for this entity have not been studied. In the present study, we carried out genetic screening in patients with remote myocardial infarction presenting with ES by next generation sequencing and identified 25 rare variants in 19 genes predominantly in RYR2, SCN5A, KCNJ11, KCNE1 and KCNH2, CACNA1B, CACNA1C, CACNA1D and desmosomal genes - DSP and DSG2 that could potentially be implicated in electrical storm. These genes have been previously reported to be associated with inherited syndromes of Sudden Cardiac Death. The present study suggests that the genetic architecture in patients with remote MI and ES of unstable ventricular tachycardia may be similar to that of Ion channelopathies. Identification of these variants may identify post MI patients who are predisposed to develop electrical storm and help in risk stratification.

Wilson disease (WD) is an inborn error of copper metabolism leading to its accumulation in liver, kidney and cornea. It is caused by a defective ATPase protein which is coded by ATP7B gene. It follows an autosomal recessive mode of inheritance with a prevalence of 1 in 30,000. WD shows varied clinical heterogeneity making clinical diagnosis a difficult task. The corneal Kayser-Fleischer (KF) ring is an important diagnostic criterion as it is invariably present in 95% of the WD cases. In this review, we discussed the varied clinical manifestations of WD which makes diagnosis a challenging process. Though genetic testing is a reliable technique to confirm clinical diagnosis, genotype-phenotype correlations are yet to be established. This could be attributed to the consanguinity and ethnic variation observed in the Indian population, suggesting genetic heterogeneity leading to clinical heterogeneity making diagnosis difficult. Further, genetic studies are warranted to establish genotype-phenotype correlations which can pave way for early diagnosis and treatment. Genetic testing will help in identifying pre-symptomatic siblings and other family members of the patient who should be advised for regular follow-up. A combination of clinical and genetic studies should be considered for proper understanding of disease manifestation and for making an early clinical diagnosis of WD. Keywords: Wilson disease; copper metabolism; genetic testing; ATP7B gene; KF ring

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Inherited cardiac disorders are clinically and genetically heterogeneous group of disorders where sudden cardiac death is mostly the first clinical presentation. The available clinical markers are insufficient to make an accurate diagnosis, and therefore, molecular genetic diagnostics is an important tool for clinical decision-making. The advancements in technology have tremendously improved the affordability of genetic testing. In India, though genetic testing is being largely applied in the pediatric settings for chromosomal abnormalities and metabolic disorders, it is still at a nascent stage in the cardiology practice. Since cardiomyopathies and channelopathies have become actionable because of new interventional therapies, this article highlights the importance and need of genetic testing for inherited cardiac disorders by practicing cardiologists, in-view of the American College of Medical Genetics, American College of Cardiology, European Heart Rhythm Association guidelines. Incorporating cardiovascular genetic testing in the routine clinical practice can take it forward by greatly improving the scope of disease management.

A Rangaraju, S Matsa Lova, N Calambur, P Nallari. Novel compound heterozygous mutations of myosin heavy chain gene in patients with hypertrophic cardiomyopathy. Curr Res Cardiol 2015;2(1):11-14.bACkgRouNd: Hypertrophic cardiomyopathy (HCM) is a multifactorial disorder, with mutations implicated in 14 sarcomeric and cytoskeletal genes, leading to genotypic and phenotypic heterogeneity, and a challenging genetic and clinical diagnosis. The genetic characteristics of HCM have been studied for more than two decades in various ethnic and racial groups, and many novel genetic variations have been reported. The myosin heavy chain gene is the most heavily implicated gene in HCM, with >200 reported mutations, the majority of which have been found in the head-rod junction. The rod portion of MYH7, coded by exons 29 to 40 and belonging to the light meromyosin (LMM) region, has not been characterized to the same extent as the head domain with respect to single-nucleotide polymorphisms (SNPs)/mutations. obJECTIVE: To screen the conserved LMM region, constituting exons 27 to 39 (13 exons), to identify any pathogenic SNPs/variations in this region in a population of Indian patients. METhodS:Molecular screening was performed by polymerase chain reaction-based single-strand conformation polymorphism analysis in 100 control individuals and 100 HCM patients. The variations were confirmed by sequencing. Insilico analysis was performed to analyze the effect of the respective variations. RESuLTS: Screening of exons 27 to 39 revealed three novel missense variations and one novel synonymous variation in exon 34. Interestingly, patients with these variations also exhibited compound heterozygosity, indicating exon 34 to be the 'hotspot' exon of the LMM region. CoNCLuSIoN:The results of the present study emphasize the importance of the LMM (rod) region of the MYH7 gene and suggest that variations in the conserved region are likely to be more pathogenic, making screening of the entire gene for HCM diagnosis mandatory.