title: The Ups and Downs of Genetic Diagnosis of Hypertrophic Cardiomyopathy.
abstract: Massive DNA sequencing, also known as next-generation sequencing, has revolutionized genetic diagnosis. This technology has reduced the effort and cost needed to analyze several genes simultaneously and has made genetic evaluation available to a larger number of patients. In hypertrophic cardiomyopathy, genetic analysis has increased from the 3 main genes implicated in the disease (MYH7, MYBPC3, TNNT2) to sequencing of more than 20 related genes. Despite the advantages of acquiring this additional information, many patients show variants of uncertain significance (mainly amino acid changes), which may also be present in at least 1 healthy control undergoing genome sequencing. This will be a dead-end situation unless the variant can be demonstrated to be associated with the disease in the patient's family. In the absence of clear evidence that these variants are truly pathogenic, they cannot be used for reliable genetic counselling in family members. Massive sequencing also enables identification of new candidate genes, but again, the problem of variants of uncertain significance limits the success of these assessments.
authors.affiliation: Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.affiliation: Cardiología-Fundación Asturcor, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Julián R
authors.initials: JR
authors.lastname: Reguero
authors.affiliation: Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain; Departamento de Medicina, Universidad de Oviedo, Oviedo, Asturias, Spain. Electronic address: eliecer.coto@sespa.es.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; D004247:DNA
keywords: Filamin C; Filamina C; Hypertrophic cardiomyopathy; Massive sequencing; Miocardiopatía hipertrófica; Secuenciación masiva; Variant of uncertain significance; Variantes de significado incierto