title: Gene-Targeted Analysis of Clinically Diagnosed Long QT Russian Families.
abstract: Long QT syndrome (LQTS) has great genetic heterogeneity: more than 500 mutations have been described in several genes. Despite many advances, a genetic diagnosis still cannot be established in 25-30% of patients. The aim of the present study was to perform genetic evaluation in 9 Russian families with LQTS; here we report the results of 4 positive probands and their relatives (a total of 16 individuals). All subjects underwent clinical examination, 12-lead ECG, and Holter monitoring. Genetic analysis of the 14 genes mainly involved in LQTS was performed using a next-generation sequencing approach. We identified two new mutations (KCNQ1 gene) and 6 known mutations (AKAP9, ANK2, KCNE1 and KCNJ2 genes) in 4 out of 9 probands, some of which have already been described in association with LQTS. Segregation studies suggest a possible causative role for KCNQ1 p.(Leu342Pro), AKAP9 p.(Arg1609Lys), KCNE1 p.(Asp85Asn), and KCNJ2 p.(Arg82Gln) variations. Our study confirmed the high genetic heterogeneity of this disease and highlights the difficulties to reveal clear pathogenic genotypes also in large pedigrees. To the best of our knowledge, this is the first genetic study of LQTS patients from Russian families.
authors.affiliation: MAGI Non-Profit Human Medical Genetics Institute.
authors.forename: Paolo Enrico
authors.initials: PE
authors.lastname: Maltese
authors.forename: Nina
authors.initials: N
authors.lastname: Orlova
authors.forename: Eugenia
authors.initials: E
authors.lastname: Krasikova
authors.forename: Elena
authors.initials: E
authors.lastname: Emelyanchik
authors.forename: Anna
authors.initials: A
authors.lastname: Cheremisina
authors.forename: Alina
authors.initials: A
authors.lastname: Kuscaeva
authors.forename: Alla
authors.initials: A
authors.lastname: Salmina
authors.forename: Roberta
authors.initials: R
authors.lastname: Miotto
authors.forename: Alice
authors.initials: A
authors.lastname: Bonizzato
authors.forename: Giulia
authors.initials: G
authors.lastname: Guerri
authors.forename: Monia
authors.initials: M
authors.lastname: Zuntini
authors.forename: Svetlana
authors.initials: S
authors.lastname: Nicoulina
authors.forename: Matteo
authors.initials: M
authors.lastname: Bertelli
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics; D000293:Adolescent; D017487:Ankyrins / Q000235:genetics; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D010375:Pedigree; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D055815:Young Adult
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; C498994:ANK2 protein, human; D017487:Ankyrins; D003598:Cytoskeletal Proteins; C489622:KCNE1 protein, human; C489457:KCNJ2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated