Publication:
Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders.

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Date

2016-04-21

Authors

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

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Public Library of Science
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BACKGROUND 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. OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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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Journal Article;

MeSH Terms

Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Elements::Metals, Alkaline Earth::Calcium
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::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::Heart Arrest::Death, Sudden, Cardiac
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Amino Alcohols::Ethanolamines::Epinephrine
Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Long QT Syndrome
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation
Medical Subject Headings::Named Groups::Persons::Parents
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Inheritance Patterns::Penetrance
Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain
Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Tachycardia::Tachycardia, Ventricular
Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Ventricular Fibrillation
Medical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Cardiac Complexes, Premature::Ventricular Premature Complexes

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Keywords

Calcio, Calmodulina, Niño, ADN, Muerte súbita cardíaca, Epinefrina, Síndrome de QT prolongado, Mutación, Padres, Penetrancia, España, Taquicardia ventricular, Fibrilación Ventricular, Complejos prematuros ventriculares

Citation

Jiménez-Jáimez J, Palomino Doza J, Ortega Á, Macías-Ruiz R, Perin F, Rodríguez-Vázquez Del Rey MM, et al. Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders. PLoS ONE. 2016; 11(4):e0153851