title: The role of clinical, genetic and segregation evaluation in sudden infant death.
abstract: Sudden infant death syndrome (SIDS) is the leading cause of death in the first year of life. Several arrhythmogenic genes have been associated with cardiac pathologies leading to infant sudden cardiac death (SCD). Our aim was to take advantage of next generation sequencing (NGS) technology to perform a thorough genetic analysis of a SIDS case. A SIDS case was referred to our institution after negative autopsy. We performed a genetic analysis of 104 SCD-related genes using a custom panel. Confirmed variants in index case were also analyzed in relatives. Clinical evaluation of first-degree family members was performed. Relatives did not show pathology. NGS identified seven variants. Two previously described as pathogenic. Four previously catalogued without clinical significance. The seventh variation was novel. Familial segregation showed that the index case's mother carried all same genetic variations except one, which was inherited from the father. The sister of the index case carried three variants. We believe that molecular autopsy should be included in current forensic protocols after negative autopsy. In addition to NGS technologies, familial genetic testing should be also performed to clarify potential pathogenic role of new variants and to identify genetic carriers at risk of SCD.
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain. Electronic address: oscar@brugada.org.
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.affiliation: Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Georgia
authors.initials: G
authors.lastname: Sarquella-Brugada
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Coll
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Mates
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Alcalde
authors.affiliation: Gendiag SL, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Ferrer-Costa
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics; D064211:Connectin / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D051191:Plakophilins / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D013398:Sudden Infant Death / Q000235:genetics*; D016596:Vinculin / Q000235:genetics
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D064211:Connectin; D003598:Cytoskeletal Proteins; C513076:EN1 protein, human; D018398:Homeodomain Proteins; C418492:KCNE3 protein, human; C495337:PKP2 protein, human; D051191:Plakophilins; D024642:Potassium Channels, Voltage-Gated; C577285:TTN protein, human; C488955:VCL protein, human; D016596:Vinculin
keywords: Custom panel; Genetics; Molecular autopsy; Next generation sequencing; SIDS