title: Targeted capture sequencing in a large LQTS family reveals a new pathogenic mutation c.2038delG in KCNH2 initially missed due to allelic dropout.
abstract: We present a new mutation in KCNH2 (c.2038delG) resulting in a frameshift and premature truncation of the IKr channel protein in a large LQTS family with several sudden death cases. This mutation was initially missed by mutation scanning with DHPLC due to allelic dropout and only retrieved after repeat genetic testing with targeted capture and massive parallel sequencing. There was full penetrance of this mutation, only if an individualized QT correction derived from 24-hour Holter data was used. This case again underscores the importance of repeat genetic testing in robust cases of LQTS that remained genotype negative with mutation scanning techniques.
authors.forename: Tomas
authors.initials: T
authors.lastname: Robyns
authors.forename: Cuno
authors.initials: C
authors.lastname: Kuiperi
authors.forename: Rik
authors.initials: R
authors.lastname: Willems
authors.forename: Anniek
authors.initials: A
authors.lastname: Corveleyn
authors.forename: Dieter
authors.initials: D
authors.lastname: Nuyens
mesh_terms: D000483:Alleles; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D004247:DNA
keywords: KCNH2; Long QT syndrome; allelic dropout; next generation sequencing; repeat genetic testing