Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing

Autores
Dionisio, Leonardo Raul; Aztiria, Eugenio Manuel; Stupniki, Sofia; Dye, Leandro; Onetto, Leonardo; Gregorietti, Franco; Keegan, Roberto; Spitzmaul, Guillermo Federico
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Long QT syndrome (LQTS) is a congenital genetic disorder that cause cardiac arrhythmia and sudden death. The genes more frequently implicated are those encoding for the K+ channels KCNQ1 (40 - 45 %) and HERG (40 – 45 %), and the Na+ channel Nav1.5 (5 – 8 %). Dysfunction in these channels leads to QT interval lengthening in ECG. Molecular identification of the causes of this disease contributes to better diagnosis, risk stratification and pharmacological treatment improvement. Our aim is to correlate clinical diagnosis with genetic variants of LQTS. We examined the LQT-associated genes KCNQ1, KCNH2 and SCN5A using gDNA extracted from 6 subjects. Five of them showed a prolonged QT interval on the ECG (>460 ms) while 1 first-degree relative presented a normal QT interval (<450 ms). The group (3 males and 3 females, 0-62 years old) included 1 with sudden cardiac death history under 40 years old and 1 with presyncope and documented polymorphic ventricular tachycardia. We amplified all exons from the 3 genes by PCR followed by sequencing. For KCNQ1 we found the uncommon variant c.1638G>A (p.Ser546=) in 2 subjects. In 1 patient we could not amplify exon 16, suggesting exon deletion. For KCNH2 we found the following variants: c.1692A>G (p.Leu564=) in 1 patient, c.1956T>C (p.Tyr652=) in 5 out of 6 cases and c.2690A>C (p.Lys897Thr) in 1 patient. Finally, we found the likely-pathogenic variant c.982C>T (p.Arg328Cys). For SCN5A no variants were detected at the tested exons. We found benign and pathological genetic variants in either KCNQ1 or KCNH2 genes of our population. No information about the exon 16 deletion for KCNQ1 as a pathological variant has been reported. To our knowledge, this is the first genetic test of LQTS performed in Argentina. Genetic characterization will impact on patient habits, avoiding risk situations such as sports, acute stress or cardiotoxic drugs therapies. Moreover, these studies will enable to set patient-oriented pharmacological treatments.
Fil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Aztiria, Eugenio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Stupniki, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Dye, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Onetto, Leonardo. Hospital Privado del Sur; Argentina
Fil: Gregorietti, Franco. Hospital Privado del Sur; Argentina
Fil: Keegan, Roberto. Hospital Privado del Sur; Argentina
Fil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
Materia
ARRHYTMIA
LQTS
KCNQ1
MUTATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/158131
Acceder
id CONICETDig_66de9e860bf006053400d9838581d2e9
oai_identifier_str oai:ri.conicet.gov.ar:11336/158131
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testingDionisio, Leonardo RaulAztiria, Eugenio ManuelStupniki, SofiaDye, LeandroOnetto, LeonardoGregorietti, FrancoKeegan, RobertoSpitzmaul, Guillermo FedericoARRHYTMIALQTSKCNQ1MUTATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Long QT syndrome (LQTS) is a congenital genetic disorder that cause cardiac arrhythmia and sudden death. The genes more frequently implicated are those encoding for the K+ channels KCNQ1 (40 - 45 %) and HERG (40 – 45 %), and the Na+ channel Nav1.5 (5 – 8 %). Dysfunction in these channels leads to QT interval lengthening in ECG. Molecular identification of the causes of this disease contributes to better diagnosis, risk stratification and pharmacological treatment improvement. Our aim is to correlate clinical diagnosis with genetic variants of LQTS. We examined the LQT-associated genes KCNQ1, KCNH2 and SCN5A using gDNA extracted from 6 subjects. Five of them showed a prolonged QT interval on the ECG (>460 ms) while 1 first-degree relative presented a normal QT interval (<450 ms). The group (3 males and 3 females, 0-62 years old) included 1 with sudden cardiac death history under 40 years old and 1 with presyncope and documented polymorphic ventricular tachycardia. We amplified all exons from the 3 genes by PCR followed by sequencing. For KCNQ1 we found the uncommon variant c.1638G>A (p.Ser546=) in 2 subjects. In 1 patient we could not amplify exon 16, suggesting exon deletion. For KCNH2 we found the following variants: c.1692A>G (p.Leu564=) in 1 patient, c.1956T>C (p.Tyr652=) in 5 out of 6 cases and c.2690A>C (p.Lys897Thr) in 1 patient. Finally, we found the likely-pathogenic variant c.982C>T (p.Arg328Cys). For SCN5A no variants were detected at the tested exons. We found benign and pathological genetic variants in either KCNQ1 or KCNH2 genes of our population. No information about the exon 16 deletion for KCNQ1 as a pathological variant has been reported. To our knowledge, this is the first genetic test of LQTS performed in Argentina. Genetic characterization will impact on patient habits, avoiding risk situations such as sports, acute stress or cardiotoxic drugs therapies. Moreover, these studies will enable to set patient-oriented pharmacological treatments.Fil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Aztiria, Eugenio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Stupniki, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Dye, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Onetto, Leonardo. Hospital Privado del Sur; ArgentinaFil: Gregorietti, Franco. Hospital Privado del Sur; ArgentinaFil: Keegan, Roberto. Hospital Privado del Sur; ArgentinaFil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaReunión Anual de Sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical SocietyFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/158131Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 86-870025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:38:09Zoai:ri.conicet.gov.ar:11336/158131instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:38:09.525CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
title Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
spellingShingle Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
Dionisio, Leonardo Raul
ARRHYTMIA
LQTS
KCNQ1
MUTATION
title_short Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
title_full Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
title_fullStr Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
title_full_unstemmed Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
title_sort Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing
dc.creator.none.fl_str_mv Dionisio, Leonardo Raul
Aztiria, Eugenio Manuel
Stupniki, Sofia
Dye, Leandro
Onetto, Leonardo
Gregorietti, Franco
Keegan, Roberto
Spitzmaul, Guillermo Federico
author Dionisio, Leonardo Raul
author_facet Dionisio, Leonardo Raul
Aztiria, Eugenio Manuel
Stupniki, Sofia
Dye, Leandro
Onetto, Leonardo
Gregorietti, Franco
Keegan, Roberto
Spitzmaul, Guillermo Federico
author_role author
author2 Aztiria, Eugenio Manuel
Stupniki, Sofia
Dye, Leandro
Onetto, Leonardo
Gregorietti, Franco
Keegan, Roberto
Spitzmaul, Guillermo Federico
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ARRHYTMIA
LQTS
KCNQ1
MUTATION
topic ARRHYTMIA
LQTS
KCNQ1
MUTATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Long QT syndrome (LQTS) is a congenital genetic disorder that cause cardiac arrhythmia and sudden death. The genes more frequently implicated are those encoding for the K+ channels KCNQ1 (40 - 45 %) and HERG (40 – 45 %), and the Na+ channel Nav1.5 (5 – 8 %). Dysfunction in these channels leads to QT interval lengthening in ECG. Molecular identification of the causes of this disease contributes to better diagnosis, risk stratification and pharmacological treatment improvement. Our aim is to correlate clinical diagnosis with genetic variants of LQTS. We examined the LQT-associated genes KCNQ1, KCNH2 and SCN5A using gDNA extracted from 6 subjects. Five of them showed a prolonged QT interval on the ECG (>460 ms) while 1 first-degree relative presented a normal QT interval (<450 ms). The group (3 males and 3 females, 0-62 years old) included 1 with sudden cardiac death history under 40 years old and 1 with presyncope and documented polymorphic ventricular tachycardia. We amplified all exons from the 3 genes by PCR followed by sequencing. For KCNQ1 we found the uncommon variant c.1638G>A (p.Ser546=) in 2 subjects. In 1 patient we could not amplify exon 16, suggesting exon deletion. For KCNH2 we found the following variants: c.1692A>G (p.Leu564=) in 1 patient, c.1956T>C (p.Tyr652=) in 5 out of 6 cases and c.2690A>C (p.Lys897Thr) in 1 patient. Finally, we found the likely-pathogenic variant c.982C>T (p.Arg328Cys). For SCN5A no variants were detected at the tested exons. We found benign and pathological genetic variants in either KCNQ1 or KCNH2 genes of our population. No information about the exon 16 deletion for KCNQ1 as a pathological variant has been reported. To our knowledge, this is the first genetic test of LQTS performed in Argentina. Genetic characterization will impact on patient habits, avoiding risk situations such as sports, acute stress or cardiotoxic drugs therapies. Moreover, these studies will enable to set patient-oriented pharmacological treatments.
Fil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Aztiria, Eugenio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Stupniki, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Dye, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Onetto, Leonardo. Hospital Privado del Sur; Argentina
Fil: Gregorietti, Franco. Hospital Privado del Sur; Argentina
Fil: Keegan, Roberto. Hospital Privado del Sur; Argentina
Fil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
description Long QT syndrome (LQTS) is a congenital genetic disorder that cause cardiac arrhythmia and sudden death. The genes more frequently implicated are those encoding for the K+ channels KCNQ1 (40 - 45 %) and HERG (40 – 45 %), and the Na+ channel Nav1.5 (5 – 8 %). Dysfunction in these channels leads to QT interval lengthening in ECG. Molecular identification of the causes of this disease contributes to better diagnosis, risk stratification and pharmacological treatment improvement. Our aim is to correlate clinical diagnosis with genetic variants of LQTS. We examined the LQT-associated genes KCNQ1, KCNH2 and SCN5A using gDNA extracted from 6 subjects. Five of them showed a prolonged QT interval on the ECG (>460 ms) while 1 first-degree relative presented a normal QT interval (<450 ms). The group (3 males and 3 females, 0-62 years old) included 1 with sudden cardiac death history under 40 years old and 1 with presyncope and documented polymorphic ventricular tachycardia. We amplified all exons from the 3 genes by PCR followed by sequencing. For KCNQ1 we found the uncommon variant c.1638G>A (p.Ser546=) in 2 subjects. In 1 patient we could not amplify exon 16, suggesting exon deletion. For KCNH2 we found the following variants: c.1692A>G (p.Leu564=) in 1 patient, c.1956T>C (p.Tyr652=) in 5 out of 6 cases and c.2690A>C (p.Lys897Thr) in 1 patient. Finally, we found the likely-pathogenic variant c.982C>T (p.Arg328Cys). For SCN5A no variants were detected at the tested exons. We found benign and pathological genetic variants in either KCNQ1 or KCNH2 genes of our population. No information about the exon 16 deletion for KCNQ1 as a pathological variant has been reported. To our knowledge, this is the first genetic test of LQTS performed in Argentina. Genetic characterization will impact on patient habits, avoiding risk situations such as sports, acute stress or cardiotoxic drugs therapies. Moreover, these studies will enable to set patient-oriented pharmacological treatments.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/158131
Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 86-87
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/158131
identifier_str_mv Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 86-87
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicina
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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