title: Genotype-phenotype correlation in long QT syndrome families.
abstract: Heterogeneity in clinical manifestations is a well-known feature in Long QT Syndrome (LQTS). The extent of this phenomenon became evident in families wherein both symptomatic and asymptomatic family members are reported. The study hence warrants genetic testing and/or screening of family members of LQTS probands for risk stratification and prediction. Of the 46 families screened, 18 probands revealed novel variations/compound heterozygosity in the gene/s screened. Families 1-4 revealed probands carrying novel variations in KCNQ1 gene along with compound heterozygosity of risk genotypes of the SCN5A, KCNE1 and NPPA gene/s polymorphisms screened. It was also observed that families- 5, 6 and 7 were typical cases of "anticipation" in which both mother and child were diagnosed with congenital LQTS (cLQTS). Families- 16 and 17 represented aLQTS probands with variations in IKs and INa encoding genes. First degree relatives (FDRs) carrying the same haplotype as the proband were also identified which may help in predictive testing and management of LQTS. Most of the probands exhibiting a family history were found to be genetic compounds which clearly points to the role of cardiac genes and their modifiers in a recessive fashion in LQTS manifestation.
authors.affiliation: Dept. of Genetics, University College of Science, Osmania University, Hyderabad 500007, Andhra Pradesh, India.
authors.forename: Sameera Fatima
authors.initials: SF
authors.lastname: Qureshi
authors.affiliation: Dept. of Genetics, University College of Science, Osmania University, Hyderabad 500007, Andhra Pradesh, India.
authors.forename: Altaf
authors.initials: A
authors.lastname: Ali
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad 500016, Andhra Pradesh, India.
authors.forename: Ananthapur
authors.initials: A
authors.lastname: Venkateshwari
authors.affiliation: Krishna Institute of Medical Sciences, 1-8-31/1, Minister Road, Secunderabad 500 003, Andhra Pradesh, India.
authors.forename: Hygriv
authors.initials: H
authors.lastname: Rao
authors.affiliation: Institute of Maternal and Child Health, Calicut Medical College, Calicut 8, Kerala, India.
authors.forename: M P
authors.initials: MP
authors.lastname: Jayakrishnan
authors.affiliation: Care Hospital, Hyderabad, Andhra Pradesh, India.
authors.forename: Calambur
authors.initials: C
authors.lastname: Narasimhan
authors.affiliation: Sri Jayadeva Institute of Cardiovascular Science and Research, Jayanagar 9th Block, Bannerghatta Road, Bangalore 560069, Karnataka, India.
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Shenthar
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, Andhra Pradesh, India.
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.affiliation: Dept. of Genetics, University College of Science, Osmania University, Hyderabad 500007, Andhra Pradesh, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nallari
keywords: Common haplotype; Compound heterozygosity; Family study; LQTS