BACKGROUND: Autosomal recessive Long QT syndrome is characterized by prolonged QTc along with congenital bilateral deafness depends on mutations in K(+) channel genes. A family of a Long QT syndrome proband from India has been identified with novel indel variations. METHODS: The molecular study of the proband revealed 4 novel indel variations in KCNQ1. In-silico analysis revealed the intronic variations has led to a change in the secondary structure of mRNA and splice site variations. The exonic variations leads to frameshift mutations. DNA analysis of the available family members revealed a carrier status. RESULTS AND CONCLUSION: It is thus predicted that the variations may lead to a change in the position of the splicing enhancer/inhibitor in KCNQ1 leading to the formation of a truncated S2-S3 fragment of KCNQ1 transmembrane protein in cardiac cells as well as epithelial cells of inner ear leading to deafness and aberrant repolarization causing prolonged QTc.
BACKGROUND:Autosomal recessive Long QT syndrome is characterized by prolonged QTc along with congenital bilateral deafness depends on mutations in K(+) channel genes. A family of a Long QT syndrome proband from India has been identified with novel indel variations. METHODS: The molecular study of the proband revealed 4 novel indel variations in KCNQ1. In-silico analysis revealed the intronic variations has led to a change in the secondary structure of mRNA and splice site variations. The exonic variations leads to frameshift mutations. DNA analysis of the available family members revealed a carrier status. RESULTS AND CONCLUSION: It is thus predicted that the variations may lead to a change in the position of the splicing enhancer/inhibitor in KCNQ1 leading to the formation of a truncated S2-S3 fragment of KCNQ1 transmembrane protein in cardiac cells as well as epithelial cells of inner ear leading to deafness and aberrant repolarization causing prolonged QTc.
Authors: I Splawski; J Shen; K W Timothy; M H Lehmann; S Priori; J L Robinson; A J Moss; P J Schwartz; J A Towbin; G M Vincent; M T Keating Journal: Circulation Date: 2000-09-05 Impact factor: 29.690
Authors: K Piippo; H Swan; M Pasternack; H Chapman; K Paavonen; M Viitasalo; L Toivonen; K Kontula Journal: J Am Coll Cardiol Date: 2001-02 Impact factor: 24.094
Authors: Arthur J Moss; Wataru Shimizu; Arthur A M Wilde; Jeffrey A Towbin; Wojciech Zareba; Jennifer L Robinson; Ming Qi; G Michael Vincent; Michael J Ackerman; Elizabeth S Kaufman; Nynke Hofman; Rahul Seth; Shiro Kamakura; Yoshihiro Miyamoto; Ilan Goldenberg; Mark L Andrews; Scott McNitt Journal: Circulation Date: 2007-04-30 Impact factor: 29.690
Authors: Jodene Eldstrom; Hongjian Xu; Daniel Werry; Congbao Kang; Matthew E Loewen; Amanda Degenhardt; Shubhayan Sanatani; Glen F Tibbits; Charles Sanders; David Fedida Journal: J Gen Physiol Date: 2010-05 Impact factor: 4.086
Authors: Peter J Schwartz; Carla Spazzolini; Lia Crotti; Jørn Bathen; Jan P Amlie; Katherine Timothy; Maria Shkolnikova; Charles I Berul; Maria Bitner-Glindzicz; Lauri Toivonen; Minoru Horie; Eric Schulze-Bahr; Isabelle Denjoy Journal: Circulation Date: 2006-02-06 Impact factor: 29.690