A homozygous SCN5A mutation in a severe, recessive type of cardiac conduction disease
β Scribed by Axel Neu; Michele Eiselt; Matthias Paul; Kathrin Sauter; Birgit Stallmeyer; Dirk Isbrandt; Eric Schulze-Bahr
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 460 KB
- Volume
- 31
- Category
- Article
- ISSN
- 1059-7794
No coin nor oath required. For personal study only.
β¦ Synopsis
Cardiac sodium channels are key players in the generation and propagation of action potentials in the human heart. Heterozygous mutations in the SCN5A gene have been found to be associated with long QT syndrome, Brugada syndrome, and sinus node dysfunction (SND). Recently, overlapping arrhythmia phenotypes have been reported as well. Here we describe a novel recessive SCN5A mutation in a family originating from the German minority in White Russia. Four affected children with a history of early cardiac arrhythmia encompassing SND, conduction disease, and severe ventricular arrhythmias, are homozygous carriers of a novel SCN5A missense mutation (p.I230T) in the channel protein. Interestingly, the heterozygous mutation carriers had neither significant ECG abnormalities nor a history of cardiac events. Heterologous expression of SCN5A(I230T) channels revealed normal protein transport but altered biophysical sodium channel properties. Voltage range of both activation and inactivation were shifted in a way that resulted in decreased sodium current and loss of channel function. In conclusion, we describe a rare clinical condition with a novel SCN5A mutation causing a new type of complex cardiac arrhythmia. Unlike most previously reported sodium channelopathies, this overlap syndrome displays recessive inheritance characteristics and does not seem to follow simple Mendelian rules.
π SIMILAR VOLUMES
We have studied a consanguineous family containing two children with severe, generalized epidermolysis bullosa simplex (EBS). Electron microscopy of skin biopsies from the affected individuals showed that basal keratinocytes were devoid of tonofilament bundles, although some single intermediate fila
Several different mutations in the glycogen-debranching enzyme gene AGL have been found in patients with glycogen storage disease type III (GSD III) to date, but no missense mutations have been reported for GSD III, only nonsense, splicing, and deletion/insertion lesions. Here we describe a novel G1
## Abstract We report on an 18βyearβold woman, born to firstβcousin parents, presenting with a severe form of anhydrotic ectodermal dysplasia (EDA/HED). She had sparse hair, absent limb hair, absent sweating, episodes of hyperpyrexia, important hypodontia, and hyperconvex nails. She also showed unu