title: HCN4 mutation as a molecular explanation on patients with bradycardia and non-compaction cardiomyopathy.
abstract: A very recent study suggested that HCN4 mutations could be associated with sinusal bradycardia and myocardial non compaction. A French family with 3 affected sisters presenting the same clinical phenotype (sinus bradycardia in combination with non compaction cardiomyopathy (NCCM)) have benefited both from a systematic cardiovascular exploration and molecular investigations. The molecular analysis, performed by NGS sequencing, led to identify only one likely-disease causing variation: p.Gly482Arg on HCN4 gene. Our results confirm the genetic evidence for the involvement of the HCN4 mutations in the combined bradycardia-NCCM phenotype and illustrates that, in front of this combined clinical phenotype, HCN4 mutations has to be suspected.
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Hospices Civils de Lyon, Lyon, France; NGS Sequencing Platform for Molecular Diagnosis, Hospices Civils de Lyon, Lyon, France; Université de Lyon, Lyon F-69003, France. Electronic address: gilles.millat@chu-lyon.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Millat
authors.affiliation: Laboratoire de Cardiogénétique Moléculaire, Hospices Civils de Lyon, Lyon, France; NGS Sequencing Platform for Molecular Diagnosis, Hospices Civils de Lyon, Lyon, France; Université de Lyon, Lyon F-69003, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Janin
authors.affiliation: Service de Cardiologie, Centre Hospitalier Emile Roux, Le Puy, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: de Tauriac
authors.affiliation: Service de Cardiologie, Centre Hospitalier Gabriel-Montpied, Clermont-Ferrand, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Roux
authors.affiliation: Service de Cardiologie, Centre Hospitalier Gabriel-Montpied, Clermont-Ferrand, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dauphin
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D001919:Bradycardia / Q000235:genetics*; D009202:Cardiomyopathies / Q000235:genetics*; D002648:Child; D005260:Female; D005820:Genetic Testing; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels
keywords: HCN4 mutations; Molecular diagnosis; Myocardial non compaction; NGS sequencing; Sinusal bradycardia