Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders
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| Název: | Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders |
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| Autoři: | Jiménez-Jáimez, Juan, Palomino Doza, Julián, Ortega, Ángeles, Macías-Ruiz, Rosa, Perin, Francesca, Rodríguez-Vázquez Del Rey, M Mar, Ortiz-Genga, Martín, Monserrat, Lorenzo, Barriales-Villa, Roberto, Blanca, Enrique, Álvarez, Miguel, Tercedor, Luis |
| Přispěvatelé: | [Jiménez-Jáimez,J, Macías-Ruiz,R, Álvarez,M, Tercedor,L] Cardiology Department, Complejo Hospitalario Universitario de Granada, Granada, Spain. Instituto de Investigación Biosanitario de Granada, Granada, Spain. [Palomino Doza,J, Ortiz-Genga,M, Monserrat,L, Barriales-Villa,R] Cardiology Department, Health in Code, A Coruña, Spain. [Ortega,A] Paediatrics Department, Hospital de Torrecárdenas, Almería, Spain. [Perin,F, Rodríguez-Vázquez Del Rey,MM, Blanca,E] Paediatrics Department, Complejo Hospitalario Universitario de Granada, Granada, Spain. |
| Zdroj: | PLoS One Digibug. Repositorio Institucional de la Universidad de Granada Universidad de Granada (UGR) RISalud-ANDALUCIA. Repositorio Institucional de Salud de Andalucía instname PLoS ONE, Vol 11, Iss 4, p e0153851 (2016) |
| Informace o vydavateli: | Public Library of Science (PLoS), 2016. |
| Rok vydání: | 2016 |
| Témata: | Male, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation, Science, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Inheritance Patterns::Penetrance, Penetrance, Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain, Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Ventricular Fibrillation, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Intracellular Calcium-Sensing Proteins::Calmodulin, Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Heart Arrest::Death, Sudden, Cardiac, Calmodulin, Cardiac Conduction System Disease, Humans, Genetic Predisposition to Disease, Child, Polymorphic Catecholaminergic Ventricular Tachycardia, Brugada Syndrome, Medical Subject Headings::Named Groups::Persons::Parents, Infant, Medical Subject Headings::Named Groups::Persons::Age Groups::Child, Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA, Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Tachycardia::Tachycardia, Ventricular, Heart Arrest, Pedigree, 3. Good health, Long QT Syndrome, Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Elements::Metals, Alkaline Earth::Calcium, Phenotype, Child, Preschool, Mutation, Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Amino Alcohols::Ethanolamines::Epinephrine, Tachycardia, Ventricular, Medicine, Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Long QT Syndrome, Female, Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Cardiac Complexes, Premature::Ventricular Premature Complexes, Research Article |
| Popis: | Calmodulin 1, 2 and 3 (CALM) mutations have been found to cause cardiac arrest in children at a very early age. The underlying aetiology described is long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and idiopathic ventricular fibrillation (IVF). Little phenotypical data about CALM2 mutations is available.The aim of this paper is to describe the clinical manifestations of the Asn98Ser mutation in CALM2 in two unrelated children in southern Spain with apparently unexplained cardiac arrest/death.Two unrelated children aged 4 and 7, who were born to healthy parents, were studied. Both presented with sudden cardiac arrest. The first was resuscitated after a VF episode, and the second died suddenly. In both cases the baseline QTc interval was within normal limits. Peripheral blood DNA was available to perform targeted gene sequencing.The surviving 4-year-old girl had a positive epinephrine test for LQTS, and polymorphic ventricular ectopic beats were seen on a previous 24-hour Holter recording from the deceased 7-year-old boy, suggestive of a possible underlying CPVT phenotype. A p.Asn98Ser mutation in CALM2 was detected in both cases. This affected a highly conserved across species residue, and the location in the protein was adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain, predicting a high pathogenic effect.Human calmodulin 2 mutation p.Asn98Ser is associated with sudden cardiac death in childhood with a variable clinical penetrance. Our results provide new phenotypical information about clinical behaviour of this mutation. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf; image/tiff; application/vnd.oasis.opendocument.text |
| Jazyk: | English |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0153851 |
| Přístupová URL adresa: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0153851&type=printable https://pubmed.ncbi.nlm.nih.gov/27100291 https://hdl.handle.net/10481/100793 http://hdl.handle.net/10668/2305 https://doaj.org/article/2ecdb7b638fd48dfa1da43b2c33b288c https://ui.adsabs.harvard.edu/abs/2016PLoSO..1153851J/abstract https://www.repositoriosalud.es/handle/10668/2305 https://core.ac.uk/display/149889992 https://pubmed.ncbi.nlm.nih.gov/27100291/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839566/ https://dx.plos.org/10.1371/journal.pone.0153851 https://hdl.handle.net/10668/2305 |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....1c7670d85319a50179dff07d3565469c |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Calmodulin 1, 2 and 3 (CALM) mutations have been found to cause cardiac arrest in children at a very early age. The underlying aetiology described is long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and idiopathic ventricular fibrillation (IVF). Little phenotypical data about CALM2 mutations is available.The aim of this paper is to describe the clinical manifestations of the Asn98Ser mutation in CALM2 in two unrelated children in southern Spain with apparently unexplained cardiac arrest/death.Two unrelated children aged 4 and 7, who were born to healthy parents, were studied. Both presented with sudden cardiac arrest. The first was resuscitated after a VF episode, and the second died suddenly. In both cases the baseline QTc interval was within normal limits. Peripheral blood DNA was available to perform targeted gene sequencing.The surviving 4-year-old girl had a positive epinephrine test for LQTS, and polymorphic ventricular ectopic beats were seen on a previous 24-hour Holter recording from the deceased 7-year-old boy, suggestive of a possible underlying CPVT phenotype. A p.Asn98Ser mutation in CALM2 was detected in both cases. This affected a highly conserved across species residue, and the location in the protein was adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain, predicting a high pathogenic effect.Human calmodulin 2 mutation p.Asn98Ser is associated with sudden cardiac death in childhood with a variable clinical penetrance. Our results provide new phenotypical information about clinical behaviour of this mutation. |
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| ISSN: | 19326203 |
| DOI: | 10.1371/journal.pone.0153851 |