title: A new approach to long QT syndrome mutation detection by Sequenom MassARRAY system.
abstract: Congenital long QT syndrome is an inherited cardiac disorder characterized by a prolonged QT interval and polymorphic ventricular arrhythmias that could result in recurrent syncope, seizures or sudden death as the most dramatic event. Until now QT interval mutations have been described in 12 genes, where the majority of mutations reside in three genes KCNQ1, KCNH2, and SCN5A. Diagnosis and prognosis are directly related with the gene and mutation involved. We have developed a diagnostic approach for long QT syndrome and Brugada syndrome based on published mutations and Sequenom MassArray system. Three diagnostic tests have been developed, oriented to each of the three most prevalent genes in the long QT syndrome. A total of 433 mutations are analyzed in 38 multiplex reactions, allowing their detection in about 48 h. Tests were validated on 502 samples from individuals with different clinical conditions and family history. The average call rates obtained for each of the tests were 93, 83, and 73% in KCNQ1, KCNH2, and SCNA, respectively. Sequenom MassARRAY mutation detection is a reliable, highly flexible, and cost-efficient alternative to conventional methods for genetic testing in long QT syndrome and Brugada syndrome, facilitating flexible upgrades of the version of the test presented here with the inclusion of new mutations.
authors.affiliation: Genomics Medicine Group, Galician Foundation of Genomic Medicine and University of Santiago de Compostela, CIBERER Santiago de Compostela, Spain.
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.forename: Rocio
authors.initials: R
authors.lastname: Gil
authors.forename: Paula
authors.initials: P
authors.lastname: Sanchez-Diz
authors.forename: María
authors.initials: M
authors.lastname: Torres
authors.forename: Inés
authors.initials: I
authors.lastname: Quintela
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: María
authors.initials: M
authors.lastname: Brión
mesh_terms: D001483:Base Sequence; D053840:Brugada Syndrome / Q000235:genetics*; D053447:Channelopathies; D004252:DNA Mutational Analysis / Q000379:methods*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D015222:Sodium Channels / Q000235:genetics
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels