Authors
Lisa M Wren, Juan Jiménez-Jáimez, Saleh Al-Ghamdi, Jumana Y Al-Aama, Amnah Bdeir, Zuhair N Al-Hassnan, Jyn L Kuan, Roger Y Foo, Franck Potet, Christopher N Johnson, Miriam C Aziz, Gemma L Carvill, Juan-Pablo Kaski, Lia Crotti, Francesca Perin, Lorenzo Monserrat, Paul W Burridge, Peter J Schwartz, Walter J Chazin, Zahurul A Bhuiyan, Alfred L George Jr
Publication date
2019/9
Journal
Circulation: Genomic and Precision Medicine
Volume
12
Issue
9
Pages
e002581
Publisher
Lippincott Williams & Wilkins
Description
Background
CaM (calmodulin) mutations are associated with congenital arrhythmia susceptibility (calmodulinopathy) and are most often de novo. In this report, we sought to broaden the genotype-phenotype spectrum of calmodulinopathies with 2 novel calmodulin mutations and to investigate mosaicism in 2 affected families.
Methods
CaM mutations were identified in 4 independent cases by DNA sequencing. Biochemical and electrophysiological studies were performed to determine functional consequences of each mutation.
Results
Genetic studies identified 2 novel CaM variants (CALM3-E141K in 2 cases; CALM1-E141V) and one previously reported CaM pathogenic variant (CALM3-D130G) among 4 probands with shared clinical features of prolonged QTc interval (range 505–725 ms) and documented ventricular arrhythmia. A fatal outcome occurred for 2 of the cases. The parents of all probands were …
Scholar articles
LM Wren, J Jiménez-Jáimez, S Al-Ghamdi, JY Al-Aama… - Circulation: Genomic and Precision Medicine, 2019