title: Sarcomeric gene mutations in sudden infant death syndrome (SIDS).
abstract: In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(®) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype.
authors.affiliation: Genetics of Cardiovascular and Ophthalmologic Diseases, Hospital-University Complex of Santiago (CHUS), Santiago de Compostela, Spain. maria.brion@usc.es
authors.forename: Maria
authors.initials: M
authors.lastname: Brion
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.forename: Montserrat
authors.initials: M
authors.lastname: Santori
authors.forename: Rocio
authors.initials: R
authors.lastname: Gil
authors.forename: Alejandro
authors.initials: A
authors.lastname: Blanco-Verea
authors.forename: Cordula
authors.initials: C
authors.lastname: Haas
authors.forename: Christine
authors.initials: C
authors.lastname: Bartsch
authors.forename: Simone
authors.initials: S
authors.lastname: Poster
authors.forename: Burkhard
authors.initials: B
authors.lastname: Madea
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D053803:Forensic Genetics; D006801:Humans; D007223:Infant; D013058:Mass Spectrometry / Q000379:methods; D009154:Mutation; D012518:Sarcomeres / Q000235:genetics*; D013398:Sudden Infant Death / Q000235:genetics*