Role of modifying genes on the severity of rare mutation of MYH7 gene in hypertrophic obstructive cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder due to mutations in sacromeric genes with variable penetrance. Hypertrophic Obstructive Cardiomyopathy (HOCM) is a major complication of Hypertrophic Cardiomyopathy. Unexplained hypertrophy in the Left Ventricle (LV) or Intraventricular Septum (IVS) had been the diagnostic criterion for HCM which is more often confirmed by the echocardiography. The frequency of HCM in general population is 1:500 and about 60-70% genetic predisposition is known. It has been observed that mutations in the Cardiac myosin binding proteinC (MYBPC3) gene causes late onset of disease with mild symptoms while mutations in the Beta Myosin Heavy chain (MYH7) gene leads to early onset with severe symptoms. Apart from Epigenetic and Environmental factors, modifier genes further complicate the situation leading to altered clinical outcome even among the same family members having identical mutation

Number needed to treat

The Number Needed To Treat (NNT) is a measure used in epidemiology to convey the effectiveness of an intervention. It is the average number of patients who need to be treated to prevent one bad outcome. It is the reverse of the Absolute Risk Reduction. The lower the NNT, the more effective the intervention. In this article we discuss the concept and limitations of this measure

Story of gene: Part II – Genetics and genomics

Living beings are encoded with the genes as a hereditary material and genetics deal with the functional and structural study of these genes. Since its discovery by Mendel, still we are struggling to completely elucidate the world, the gene, and its interactions. From pea plant experiments to human genome, numbers of eminent scientists had given their contributions in understanding the vast galaxy of genetic nodes in the genome. With the DNA technology advancement, in the near future, we may able to understand molecular mechanisms of human body leading to customized medicines termed as personalized medicine. In this article, we had taken further the story of gene part I to extend our acquaintance before human genetics. We had also given special context to Indian scientist making remarkable achievement in the field of genetics and genomics

Profile of serpiginous choroiditis in a tertiary eye care centre in eastern India

Purpose: To study the clinical profile of serpiginous choroiditis in eastern India. Materials and Methods: Ninety-one eyes of 54 patients with serpiginous choroiditis presenting to a tertiary care centre in eastern India between January 2006 and December 2010 were included in the study. Clinical presentation, treatment given, and visual outcome of the eyes were studied. Results: Thirty-five (64.8%) patients were male and 19 (35.2%) were female in the age group of 13-62 years (mean age: 34.1 μ 18.7 years). Blurring of vision (71; 78%) and floaters (36; 39.5%) were commonest symptoms. In 75 (82.4%) eyes, choroiditis started from optic nerve head and spreading centrifugally. Overall, 38 (41.75%) eyes had macular involvement at first visit. Mantoux test reading was 10 mm or more (Group A) in 12 (22.22%) patients and less than 10 mm (Group B) in 42 (77.77%) patients. Difference between Groups A and B in macular involvement at first visit (10; 50% vs. 28; 39.4%) and rate of recurrence (3; 15% vs. 14; 19.7%) was not statistically significant (P = 0.37 and 0.68). Oral steroid (51; 94.4%) was the commonest mode of treatment. Fifty-one (56%) eyes had two lines or more improvement in vision. Conclusions: The present study details the clinical presentation, treatment, and visual outcome of serpiginous choroiditis. Mantoux test reading does not affect the clinical presentation or the treatment outcome in these eyes

Iatrogenc hypothyroidism: A consequence of external beam radiotherapy to the head & neck malignancies

Background: Hypothyroidism is a known consequence of external beam radiotherapy to the neck encompassing part or whole of the thyroid gland for over 40 years. Still thyroid function tests are not a part of routine follow up of head - neck cancer patients treated with radiotherapy with or without surgery and / or chemotherapy. Aim: Aim of this study was to find out the incidence of hypothyroidism in head - neck cancer patients treated with radiotherapy with or without chemotherapy where radiation portals included most or whole of the thyroid gland. Materials and Methods: From September 2001 to November 2003, 187 patients with head-neck malignancies were treated with external beam radiotherapy whose radiation portals included part or whole of the thyroid gland with / without chemotherapy. Thyroid function tests were done at the beginning of treatment, at six weeks after completion of radiotherapy and thereafter at six weeks interval for two years. Results: Out of 187 patients, five were excluded from the study as they were found to be hypothyroid before the initiation of treatment. Another four were excluded from result analysis because they underwent laryngectomy for uncontrolled disease. Of the patients attending the follow up clinic, 17.8 % and 21.8 % were found to have clinical and sub-clinical hypothyroidism at two year. Conclusion: As a significant number of patients develop hypothyroidism following radiotherapy to the neck, thyroid function tests should be included in the routine follow up protocol of such patients. But certain questions have emerged from this study which need a large randomized study to find out the answers

Epidemiology of cardiomyopathy - A clinical and genetic study of hypertrophic cardiomyopathy: The EPOCH-H study

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder with the prevalence of 1 in 500 globally. HCM is clinically characterized by thickening of the wall of the heart, predominantly left ventricle (LV), and interventricular septum (IVS). Our study aims to report the demographical, clinical and genetic profile of Indian HCM patients. Methods: HCM patients were recruited on the basis of WHO criteria. The clinical phenotypes were analyzed using electrocardiography, two-dimensional electrocardiography, and hotspot region of the MYH7 gene was sequenced for all patients as well as for controls. Results: There were 59 patients with a clinical diagnosis of HCM with a preponderance of disease in males with a ratio (men, women) of 5.5:1. Average age of onset of the disease was late 30 s (39.2 ± 14.5) with familial HCM accounting for 18% (n = 9) for total HCM families (n = 50). Nonobstructive kind of HCM was more prevalent as compared to obstructive HCM (66.1% vs. 33.9%). Average posterior wall LV thickness of the HCM patients was 16 ± 4.8 mm and IVS thickness was 21 ± 8.3 mm with familial patients having greater wall thickness as compared to sporadic patients. Sequencing of hotspot region of MYH7 identified three mutations in three different patients. Two mutations were found to be segregating in familial cases. Conclusion: HCM is more prevalent in males with a predominance of hypertrophic nonobstructive cardiomyopathy form. Eighteen percent of cases were familial and showed an early onset of the disease and worse prognosis as compared to sporadic cases. Hotspot sequencing of MYH7 only explains 6% of its genetic basis. More of the candidate genes need to be screened through advanced techniques like next generation sequencing to identify the causal genes which could make us understand the mechanistic pathways

Epidemiology of cardiomyopathy - A clinical and genetic study of dilated cardiomyopathy: The EPOCH-D study

Background: Dilated Cardiomyopathy (DCM) is a genetic disorder where a heterogeneous group of cardiac-muscles are involved and is characterized by ventricular dilatation, impaired systolic function, reduced myocardial contractility with left ventricular ejection fraction (LVEF) less than 40%. Our study aims to report the Demographic, Clinical and Genetic profile of Indian Dilated Cardiomyopathy patients. Methodology: All patients were recruited with prior written informed consent and are of Indian origin. Results: In a total of 80 DCM patients, the prevalence was higher among males. In males, mean age of onset was comparatively less than females. In this cohort, 40% had familial inheritance. Sixty two percent of DCM patients belong to NYHA functional class II with ejection fraction (EF) ranging between 21-30% and, around one third of the patients had atrial fibrillation (AF). Genetic screening revealed a novel splice site mutation LMNA (c.639+ G>C) and a rare variant MYH7 (c.2769 C>T) in a patient and insilico analysis of both variants suggested functional changes that were considered pathogenic. We report 3% and 4% occurance of variants, each in LMNA and MYH7, where as reported frequencies of these genes are 6% LMNA and 4% MYH7. Conclusions: DCM is often familial and all possible candidate genes should be screened to identify mutations. Such type of exercise may help in the identification of mechanistic pathways. Next generation sequencing platforms may play an important role in this respect in future

Epidemiology of cardiomyopathy – A clinical and genetic study of restrictive cardiomyopathy: The EPOCH-R study

Introduction: Restrictive cardiomyopathy (RCM) is characterized by diastolic dysfunction, biatrial enlargement, and normal or near-normal systolic function. RCM is the rarest kind among cardiomyopathies with a severe outcome. Methods: Here, we present the clinical outcomes of thirty RCM patients recruited from a tertiary care unit of India, All India Institute of Medical Sciences, New Delhi. For clinical assessment, patients underwent electrocardiogram, echocardiography, and cardiac catheterization, and endomyocardial biopsy whenever required. Results: Out of 190 patients with cardiomyopathy, 100 had dilated cardiomyopathy, 60 had hypertrophic cardiomyopathy, and 30 had idiopathic RCM and were recruited for the study. Out of these thirty patients, 63.3% were males. A maximum number of patients were diagnosed in their second to third decade of life. Atrial fibrillation (73.3%) and ST-T abnormalities (76.6%) were common. Most of the patients showed the early age of onset with symptoms emerging in the first and second decades of life. Shortness of breath and fatigue were found to be common symptoms. No familial cases were found. Conclusion: RCM in India is a sporadic disease, rare, and occurs in the young. Prognosis of RCM is still worse than any other cardiomyopathy