Long QT syndrome type 1 (LQT1) is the most common type of all Long QT syndromes (LQTS) and occurs due to mutations in KCNQ1. Biallelic mutations with deafness is called Jervell and Lange-Nielsen syndrome (JLNS) and without deafness is autosomal recessive Romano-Ward syndrome (AR RWS). In this prospective study, we report biallelic mutations in KCNQ1 in Indian patients with LQT1 syndrome. Forty patients with a clinical diagnosis of LQT1 syndrome were referred for molecular testing. Of these, 18 were excluded from the analysis as they did not fulfill the inclusion criteria of broad T wave ECG pattern of the study. Direct sequencing of KCNQ1 was performed in 22 unrelated probands, parents and at-risk family members. Mutations were identified in 17 patients, of which seven had heterozygous mutations and were excluded in this analysis. Biallelic mutations were identified in 10 patients. Five of 10 patients did not have deafness and were categorized as AR RWS, the rest being JLNS. Eight mutations identified in this study have not been reported in the literature and predicted to be pathogenic by in silico analysis. We hypothesize that the homozygous biallelic mutations identified in 67% of families was due to endogamous marriages in the absence of consanguinity. This study presents biallelic gene mutations in KCNQ1 in Asian Indian patients with AR JLNS and RWS. It adds to the scant worldwide literature of mutation studies in AR RWS. © 2016 Wiley Periodicals, Inc.

BackgroundLong QT syndromes (LQTS) are characterized by prolonged QTc interval on electrocardiogram (ECG) and manifest with syncope, seizures or sudden cardiac death. Long QT 1–3 constitute about 75% of all inherited LQTS. We classified a cohort of Indian patients for the common LQTS based on T wave morphology and triggering factors to prioritize the gene to be tested. We sought to identify the causative mutations and mutation spectrum, perform genotype-phenotype correlation and screen family members.MethodsThirty patients who fulfilled the criteria were enrolled. The most probable candidate gene among KCNQ1, KCNH2 and SCN5A were sequenced.ResultsOf the 30 patients, 22 were classified at LQT1, two as LQT2 and six as LQT3. Mutations in KCNQ1 were identified in 17 (77%) of 22 LQT1 patients, KCNH2 mutation in one of two LQT2 and SCN5A mutations in two of six LQT3 patients. We correlated the presence of the specific ECG morphology in all mutation positive cases. Eight mutations in KCNQ1 and one in SCN5A were novel and predicted to be pathogenic by in-silico analysis. Of all parents with heterozygous mutations, 24 (92%) of 26 were asymptomatic. Ten available siblings of nine probands were screened and three were homozygous and symptomatic, five heterozygous and asymptomatic.ConclusionsThis study in a cohort of Asian Indian patients highlights the mutation spectrum of common Long QT syndromes. The clinical utility for prevention of unexplained sudden cardiac deaths is an important sequel to identification of the mutation in at-risk family members.

Background & Objectives Mutations in Bcr-Abl gene is responsible for resistance after Imatinib treatment in 30-60% of the cases. Currently the data does not support testing for these mutations in Imatinib naïve cases. However there is a data emerging that suggest that base line mutations in the Bcr-Abl gene do exist even before Imatinib is started, especially in patients with high SOKAL score. In India the failure rate of Imatinib is higher in comparison to western literature because patients are detected for CML chronic phase (CP) at a later stage. This study was designed to identify mutations in Abl-KD in Indian CML patients with no previous exposure to tyrosine kinase inhibitor. Methods This study targeted a cohort of CML-CP patients (n=47) without prior TKI exposure. KD mutations were analyzed by direct sequencing. Results A total of 47 samples were evaluated, out of which 2 samples were identified to have the same variation. This heterozygous missense variation (A206D) in the Abl1 gene was located on SH2 domain of Exon 4. The change was from C>A in codon 206, which caused a protein change from Alanine to Aspartic acid (p.A206D). By using the mutation taster software, this change was predicted to be disease causing with a high probability of .99 (∞1). One of the patients died within one year of diagnosis in spite of imatinib treatment. Interpretation & conclusion A novel mutation with putative pathogenicity was identified in the TKI-naïve Indian CML patients, supporting the concept that naturally occurring KD mutations are present in leukemic cell prior to drug exposure. Disclosures: No relevant conflicts of interest to declare.

The basic aim of the paper was to investigate various new prototypes of aortic valves. The fabricated valve prototypes were then tested by various hydrodynamic and hemocompatibility.tests The various prototype values designed and fabricated were (1) bileaflet valve (2) conical poppet valve (3) disc poppet valve and (4) a fluidic nozzle valve. These valves were tested for percentage regurgitation across them, pressure drop in steady flow, flow visualization in steady and pulsatile flows and for hemocompatibility. The poppet valves had a low percentage of regurgitation, and at higher heart rates, the fluidic nozzle diode was very competent. The study and results, serve at best, as guidelines for future research work in the field. The fluidic nozzle diode by its very form appears very promising in the mitral area.