<i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort
Long QT syndrome (LQTS) is an inherited (autosomal dominant) channelopathy associated with susceptibility to ventricular arrhythmias due to malfunction of ion channels in cardiomyocytes, that could lead to sudden death (SD). Most pathogenic variants are in the main 3 genes: <i>KCNQ1 (LQT1)<...
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MDPI AG
2022-04-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/4/556 |
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| author | Rebeca Lorca Alejandro Junco-Vicente Alicia Pérez-Pérez Isaac Pascual Yvan Rafael Persia-Paulino Francisco González-Urbistondo Elías Cuesta-Llavona Bárbara C. Fernández-Barrio César Morís José Manuel Rubín Eliecer Coto Juan Gómez José Julián Rodríguez Reguero |
| author_facet | Rebeca Lorca Alejandro Junco-Vicente Alicia Pérez-Pérez Isaac Pascual Yvan Rafael Persia-Paulino Francisco González-Urbistondo Elías Cuesta-Llavona Bárbara C. Fernández-Barrio César Morís José Manuel Rubín Eliecer Coto Juan Gómez José Julián Rodríguez Reguero |
| author_sort | Rebeca Lorca |
| collection | DOAJ |
| description | Long QT syndrome (LQTS) is an inherited (autosomal dominant) channelopathy associated with susceptibility to ventricular arrhythmias due to malfunction of ion channels in cardiomyocytes, that could lead to sudden death (SD). Most pathogenic variants are in the main 3 genes: <i>KCNQ1 (LQT1)</i>, <i>KCNH2 (LQT2)</i> and <i>SCN5A (LQT3)</i>. Efforts to improve the understanding of the genotype-phenotype relationship are essential to improve the medical clinical practice. In this study, we identified all index patients referred for NGS genetic sequencing due to LQTS, in a Spanish cohort, who were carriers of a new pathogenic variant (<i>KCNH2</i> p.Gly262AlafsTer98). Genetic and clinical family screening was performed in order to describe its phenotypic characteristics. We identified 22 relatives of Romani ethnicity, who were carriers of the variant. Penetrance reached a 100% and adherence to medical treatment was low. There was a high rate of clinical events, particularly arrhythmic events and SD (1 in every 4 patients presented syncope, 1 presented an aborted SD, 2 obligated carriers suffered SD before the age of 40 and 4 out of 6 carriers of an implantable cardioverter-defibrillator (ICD) had appropriate ICD therapies. Correct adherence to medical treatment in all carriers should be specially encouraged in this population. ICD implantation decision in non-compliant patients, and refusing left cardiac sympathetic denervation, should be carefully outweighed. |
| first_indexed | 2024-03-09T04:29:25Z |
| format | Article |
| id | doaj.art-16bb434408664ee684f9a719c7e280d3 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T04:29:25Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-16bb434408664ee684f9a719c7e280d32023-12-03T13:37:15ZengMDPI AGLife2075-17292022-04-0112455610.3390/life12040556<i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish CohortRebeca Lorca0Alejandro Junco-Vicente1Alicia Pérez-Pérez2Isaac Pascual3Yvan Rafael Persia-Paulino4Francisco González-Urbistondo5Elías Cuesta-Llavona6Bárbara C. Fernández-Barrio7César Morís8José Manuel Rubín9Eliecer Coto10Juan Gómez11José Julián Rodríguez Reguero12Unidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainHeart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainPediatric Area, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainHeart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainHeart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainHeart Area, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainUnidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainPediatric Area, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainUnidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainUnidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainUnidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainUnidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainUnidad de Referencia de Cardiopatías Familiares-HUCA, Área del Corazón y Departamento de Genética Molecular, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainLong QT syndrome (LQTS) is an inherited (autosomal dominant) channelopathy associated with susceptibility to ventricular arrhythmias due to malfunction of ion channels in cardiomyocytes, that could lead to sudden death (SD). Most pathogenic variants are in the main 3 genes: <i>KCNQ1 (LQT1)</i>, <i>KCNH2 (LQT2)</i> and <i>SCN5A (LQT3)</i>. Efforts to improve the understanding of the genotype-phenotype relationship are essential to improve the medical clinical practice. In this study, we identified all index patients referred for NGS genetic sequencing due to LQTS, in a Spanish cohort, who were carriers of a new pathogenic variant (<i>KCNH2</i> p.Gly262AlafsTer98). Genetic and clinical family screening was performed in order to describe its phenotypic characteristics. We identified 22 relatives of Romani ethnicity, who were carriers of the variant. Penetrance reached a 100% and adherence to medical treatment was low. There was a high rate of clinical events, particularly arrhythmic events and SD (1 in every 4 patients presented syncope, 1 presented an aborted SD, 2 obligated carriers suffered SD before the age of 40 and 4 out of 6 carriers of an implantable cardioverter-defibrillator (ICD) had appropriate ICD therapies. Correct adherence to medical treatment in all carriers should be specially encouraged in this population. ICD implantation decision in non-compliant patients, and refusing left cardiac sympathetic denervation, should be carefully outweighed.https://www.mdpi.com/2075-1729/12/4/556long QT syndrome<i>KCNH2</i> geneinheritable arrhythmogenic disordergenetic testing |
| spellingShingle | Rebeca Lorca Alejandro Junco-Vicente Alicia Pérez-Pérez Isaac Pascual Yvan Rafael Persia-Paulino Francisco González-Urbistondo Elías Cuesta-Llavona Bárbara C. Fernández-Barrio César Morís José Manuel Rubín Eliecer Coto Juan Gómez José Julián Rodríguez Reguero <i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort Life long QT syndrome <i>KCNH2</i> gene inheritable arrhythmogenic disorder genetic testing |
| title | <i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort |
| title_full | <i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort |
| title_fullStr | <i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort |
| title_full_unstemmed | <i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort |
| title_short | <i>KCNH2</i> p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort |
| title_sort | i kcnh2 i p gly262alafster98 a new threatening variant associated with long qt syndrome in a spanish cohort |
| topic | long QT syndrome <i>KCNH2</i> gene inheritable arrhythmogenic disorder genetic testing |
| url | https://www.mdpi.com/2075-1729/12/4/556 |
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