Cargando…
Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome
Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 (KCNH2) and LQTS3 (SCN5A) are considered to be a greater risk of LAEs than LQTS1 (KCNQ1) patients. Gender differences are also impo...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760054/ https://www.ncbi.nlm.nih.gov/pubmed/33256261 http://dx.doi.org/10.3390/jcm9123846 |
_version_ | 1783627241703342080 |
---|---|
author | Lorca, Rebeca Junco-Vicente, Alejandro Martin-Fernandez, Maria Pascual, Isaac Aparicio, Andrea Barja, Noemi Cuesta-LLavona, Elias Roces, Luis Avanzas, Pablo Moris, Cesar Coto, Eliecer Rodríguez Reguero, José Julían Gómez, Juan |
author_facet | Lorca, Rebeca Junco-Vicente, Alejandro Martin-Fernandez, Maria Pascual, Isaac Aparicio, Andrea Barja, Noemi Cuesta-LLavona, Elias Roces, Luis Avanzas, Pablo Moris, Cesar Coto, Eliecer Rodríguez Reguero, José Julían Gómez, Juan |
author_sort | Lorca, Rebeca |
collection | PubMed |
description | Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 (KCNH2) and LQTS3 (SCN5A) are considered to be a greater risk of LAEs than LQTS1 (KCNQ1) patients. Gender differences are also important. Series analyzing families with the same pathogenic variants may help in the progress of elaborating strong specific genotype-phenotype management strategies. In this manuscript, we describe the phenotype of seven unrelated families, carriers of the KCNQ1 G168R pathogenic variant. Methods: we identified all consecutive index cases referred for genetic testing with LQTS diagnosis carriers of KCNQ1 G168R variant. Genetic and clinical screening for all available relatives was performed. Results: we evaluated seven unrelated families, with a total 34 KCNQ1 G168R carriers (two obligated carriers died without available EKGs to evaluate the phenotype). All index cases but one were women and three of them presented with aborted sudden cardiac death (SCD) or syncope. The presence of sudden death in these families is notable, with a total of nine unexplained sudden deaths and four aborted SCD. Phenotype penetrance was 100% in women and 37.5% in men. Conclusions: KCNQ1 G168R is a pathogenic variant, with a high penetrance among women and mild penetrance among men. Risk for LAEs in this variant seems not negligible, especially among woman, and risk stratification should always be carefully evaluated. |
format | Online Article Text |
id | pubmed-7760054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77600542020-12-26 Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome Lorca, Rebeca Junco-Vicente, Alejandro Martin-Fernandez, Maria Pascual, Isaac Aparicio, Andrea Barja, Noemi Cuesta-LLavona, Elias Roces, Luis Avanzas, Pablo Moris, Cesar Coto, Eliecer Rodríguez Reguero, José Julían Gómez, Juan J Clin Med Article Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 (KCNH2) and LQTS3 (SCN5A) are considered to be a greater risk of LAEs than LQTS1 (KCNQ1) patients. Gender differences are also important. Series analyzing families with the same pathogenic variants may help in the progress of elaborating strong specific genotype-phenotype management strategies. In this manuscript, we describe the phenotype of seven unrelated families, carriers of the KCNQ1 G168R pathogenic variant. Methods: we identified all consecutive index cases referred for genetic testing with LQTS diagnosis carriers of KCNQ1 G168R variant. Genetic and clinical screening for all available relatives was performed. Results: we evaluated seven unrelated families, with a total 34 KCNQ1 G168R carriers (two obligated carriers died without available EKGs to evaluate the phenotype). All index cases but one were women and three of them presented with aborted sudden cardiac death (SCD) or syncope. The presence of sudden death in these families is notable, with a total of nine unexplained sudden deaths and four aborted SCD. Phenotype penetrance was 100% in women and 37.5% in men. Conclusions: KCNQ1 G168R is a pathogenic variant, with a high penetrance among women and mild penetrance among men. Risk for LAEs in this variant seems not negligible, especially among woman, and risk stratification should always be carefully evaluated. MDPI 2020-11-26 /pmc/articles/PMC7760054/ /pubmed/33256261 http://dx.doi.org/10.3390/jcm9123846 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lorca, Rebeca Junco-Vicente, Alejandro Martin-Fernandez, Maria Pascual, Isaac Aparicio, Andrea Barja, Noemi Cuesta-LLavona, Elias Roces, Luis Avanzas, Pablo Moris, Cesar Coto, Eliecer Rodríguez Reguero, José Julían Gómez, Juan Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome |
title | Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome |
title_full | Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome |
title_fullStr | Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome |
title_full_unstemmed | Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome |
title_short | Clinical Implications and Gender Differences of KCNQ1 p.Gly168Arg Pathogenic Variant in Long QT Syndrome |
title_sort | clinical implications and gender differences of kcnq1 p.gly168arg pathogenic variant in long qt syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760054/ https://www.ncbi.nlm.nih.gov/pubmed/33256261 http://dx.doi.org/10.3390/jcm9123846 |
work_keys_str_mv | AT lorcarebeca clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT juncovicentealejandro clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT martinfernandezmaria clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT pascualisaac clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT aparicioandrea clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT barjanoemi clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT cuestallavonaelias clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT rocesluis clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT avanzaspablo clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT moriscesar clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT cotoeliecer clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT rodriguezreguerojosejulian clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome AT gomezjuan clinicalimplicationsandgenderdifferencesofkcnq1pgly168argpathogenicvariantinlongqtsyndrome |