Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders
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{"title"=>"Calmodulin 2 mutation N98S is associated with unexplained cardiac arrest in infants due to low clinical penetrance electrical disorders", "type"=>"journal", "authors"=>[{"first_name"=>"Juan", "last_name"=>"Jiménez-Jáimez", "scopus_author_id"=>"7801478670"}, {"first_name"=>"Julián Palomino", "last_name"=>"Doza", "scopus_author_id"=>"55328374300"}, {"first_name"=>"Ángeles", "last_name"=>"Ortega", "scopus_author_id"=>"57189029892"}, {"first_name"=>"Rosa", "last_name"=>"Macías-Ruiz", "scopus_author_id"=>"26030007200"}, {"first_name"=>"Francesca", "last_name"=>"Perin", "scopus_author_id"=>"55510719600"}, {"first_name"=>"M. Mar", "last_name"=>"Rodríguez-Vázquez Del Rey", "scopus_author_id"=>"6507831335"}, {"first_name"=>"Martín", "last_name"=>"Ortiz-Genga", "scopus_author_id"=>"56054853500"}, {"first_name"=>"Lorenzo", "last_name"=>"Monserrat", "scopus_author_id"=>"6701492113"}, {"first_name"=>"Roberto", "last_name"=>"Barriales-Villa", "scopus_author_id"=>"7004262971"}, {"first_name"=>"Enrique", "last_name"=>"Blanca", "scopus_author_id"=>"57189025870"}, {"first_name"=>"Miguel", "last_name"=>"Álvarez", "scopus_author_id"=>"35473980200"}, {"first_name"=>"Luis", "last_name"=>"Tercedor", "scopus_author_id"=>"6603579058"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"610063655", "sgr"=>"84964733152", "issn"=>"19326203", "pmid"=>"27100291", "scopus"=>"2-s2.0-84964733152", "doi"=>"10.1371/journal.pone.0153851"}, "id"=>"bb4d75ea-31e7-35c4-9f6e-4b733addea95", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/calmodulin-2-mutation-n98s-associated-unexplained-cardiac-arrest-infants-due-low-clinical-penetrance", "reader_count"=>21, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>4, "Sports and Recreations"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>5}}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/5000677", "https://ndownloader.figshare.com/files/5000683"], "description"=>"<div><p>Background</p><p>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.</p><p>Objectives</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div>", "links"=>[], "tags"=>["arrest", "Little phenotypical data", "baseline QTc interval", "Calmodulin 2 Mutation N 98S", "Conclusions Human calmodulin 2 mutation p.Asn 98Ser", "Peripheral blood DNA", "LQTS", "IVF", "CALM 2 mutations", "CALM 2", "Asn 98Ser mutation", "calcium binding loops", "Unexplained Cardiac Arrest", "VF", "CPVT", "p.Asn 98Ser mutation"], "article_id"=>3195280, "categories"=>["Medicine", "Genetics", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Juan Jiménez-Jáimez", "Julián Palomino Doza", "Ángeles Ortega", "Rosa Macías-Ruiz", "Francesca Perin", "M. Mar Rodríguez-Vázquez del Rey", "Martín Ortiz-Genga", "Lorenzo Monserrat", "Roberto Barriales-Villa", "Enrique Blanca", "Miguel Álvarez", "Luis Tercedor"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0153851.s001", "https://dx.doi.org/10.1371/journal.pone.0153851.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Calmodulin_2_Mutation_N98S_Is_Associated_with_Unexplained_Cardiac_Arrest_in_Infants_Due_to_Low_Clinical_Penetrance_Electrical_Disorders/3195280", "title"=>"Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-04-21 06:01:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/5000707"], "description"=>"<p>A: Pedigree analysis, ECG and 24-hour Holter analysis of the deceased 7-year-old male proband, with sinus bradycardia on the ECG, 432 ms QTc interval and extrasystolic ventricular bigeminy on the Holter-ECG. B: Pedigree analysis, epinephrine test and record of ventricular fibrillation during cardiac arrest of the 4-year-old female patient who survived. Note the prolonged 36 ms absolute QT interval after the dose of adrenaline.</p>", "links"=>[], "tags"=>["arrest", "Little phenotypical data", "baseline QTc interval", "Calmodulin 2 Mutation N 98S", "Conclusions Human calmodulin 2 mutation p.Asn 98Ser", "Peripheral blood DNA", "LQTS", "IVF", "CALM 2 mutations", "CALM 2", "Asn 98Ser mutation", "calcium binding loops", "Unexplained Cardiac Arrest", "VF", "CPVT", "p.Asn 98Ser mutation"], "article_id"=>3195304, "categories"=>["Medicine", "Genetics", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Juan Jiménez-Jáimez", "Julián Palomino Doza", "Ángeles Ortega", "Rosa Macías-Ruiz", "Francesca Perin", "M. Mar Rodríguez-Vázquez del Rey", "Martín Ortiz-Genga", "Lorenzo Monserrat", "Roberto Barriales-Villa", "Enrique Blanca", "Miguel Álvarez", "Luis Tercedor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153851.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Clinical_images_of_both_cases_/3195304", "title"=>"Clinical images of both cases.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-21 06:01:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/5000797"], "description"=>"<p>Clinical characteristics of the 2 probands (CPVT: Cathecolaminergic Polymorphic Ventricular Tachycardia; VF: idiopathic ventricular fibrillation; LQTS: Long QT Syndrome; SCD: sudden cardiac death; VE: ventricular extrasystole).</p>", "links"=>[], "tags"=>["arrest", "Little phenotypical data", "baseline QTc interval", "Calmodulin 2 Mutation N 98S", "Conclusions Human calmodulin 2 mutation p.Asn 98Ser", "Peripheral blood DNA", "LQTS", "IVF", "CALM 2 mutations", "CALM 2", "Asn 98Ser mutation", "calcium binding loops", "Unexplained Cardiac Arrest", "VF", "CPVT", "p.Asn 98Ser mutation"], "article_id"=>3195379, "categories"=>["Medicine", "Genetics", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Juan Jiménez-Jáimez", "Julián Palomino Doza", "Ángeles Ortega", "Rosa Macías-Ruiz", "Francesca Perin", "M. Mar Rodríguez-Vázquez del Rey", "Martín Ortiz-Genga", "Lorenzo Monserrat", "Roberto Barriales-Villa", "Enrique Blanca", "Miguel Álvarez", "Luis Tercedor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153851.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Clinical_characteristics_of_the_2_probands_CPVT_Cathecolaminergic_Polymorphic_Ventricular_Tachycardia_VF_idiopathic_ventricular_fibrillation_LQTS_Long_QT_Syndrome_SCD_sudden_cardiac_death_VE_ventricular_extrasystole_/3195379", "title"=>"Clinical characteristics of the 2 probands (CPVT: Cathecolaminergic Polymorphic Ventricular Tachycardia; VF: idiopathic ventricular fibrillation; LQTS: Long QT Syndrome; SCD: sudden cardiac death; VE: ventricular extrasystole).", "pos_in_sequence"=>4, "defined_type"=>3, "published_date"=>"2016-04-21 06:01:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/5000743"], "description"=>"<p>A. Schematic view of the CALM2 gene. The red line marks the approximate location of the mutation. B. Correlation with the cDNA. The affected codon is shown in a square. C. Electropherogram of the patient showing the A>G substitution D. Protein alignments showing the Asn98 conservation across species. E. CALM2 protein sequence. Exons are shown in alternate black/blue colours. EF-hand motifs are shown in bold and underlined. Asn98 are shown in red. Note the location of the mutation at the third EF-hand motif.</p>", "links"=>[], "tags"=>["arrest", "Little phenotypical data", "baseline QTc interval", "Calmodulin 2 Mutation N 98S", "Conclusions Human calmodulin 2 mutation p.Asn 98Ser", "Peripheral blood DNA", "LQTS", "IVF", "CALM 2 mutations", "CALM 2", "Asn 98Ser mutation", "calcium binding loops", "Unexplained Cardiac Arrest", "VF", "CPVT", "p.Asn 98Ser mutation"], "article_id"=>3195334, "categories"=>["Medicine", "Genetics", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Juan Jiménez-Jáimez", "Julián Palomino Doza", "Ángeles Ortega", "Rosa Macías-Ruiz", "Francesca Perin", "M. Mar Rodríguez-Vázquez del Rey", "Martín Ortiz-Genga", "Lorenzo Monserrat", "Roberto Barriales-Villa", "Enrique Blanca", "Miguel Álvarez", "Luis Tercedor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153851.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/View_of_the_p_Asn98Ser_mutation_/3195334", "title"=>"View of the p.Asn98Ser mutation.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-21 06:01:41"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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