Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations
Howard Hughes Medical Institute · Harvard University · +2 more institutions
Abstract
Timothy syndrome (TS) is a multisystem disorder that causes syncope and sudden death from cardiac arrhythmias. Prominent features include congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. All TS individuals have syndactyly (webbing of fingers and toes). We discovered that TS resulted from a recurrent, de novo cardiac L-type calcium channel (CaV1.2) mutation, G406R. G406 is located in alternatively spliced exon 8A, encoding transmembrane segment S6 of domain I. Here, we describe two individuals with a severe variant of TS (TS2). Neither child had syndactyly. Both individuals had extreme prolongation of the QT interval on electrocardiogram, with a QT…
Citation impact
- FWCI
- 18.24
- Percentile
- 100%
- References
- 27
Authors
8- ISIgor SplawskiCorresponding
Howard Hughes Medical Institute, Harvard University
- KWKatherine W. Timothy
Howard Hughes Medical Institute, Harvard University, Harvard University Press
- NDNiels Decher
Howard Hughes Medical Institute, Harvard University
- PKPradeep Kumar
Howard Hughes Medical Institute, Harvard University
- FBFrank B. Sachse
Howard Hughes Medical Institute, Harvard University, Bioengineering Center
Topics & keywords
- Afterdepolarization
- Exon
- Sudden death
- Missense mutation
- QT interval
- Cav1.2
- Mutation
- Long QT syndrome
- Good health and well-being