JPH2 p.(Thr161Lys) is a Finnish founder mutation associating to hypertrophic cardiomyopathy with or without systolic heart failure and conduction abnormalities
Nov 30, 2018


During the last two decades, variants in the sarcomere genes have been found to comprise the most common cause for hypertrophic cardiomyopathy (HCM). However, a significant number of patients with dominant HCM are left without a molecular genetic diagnosis. Next generation sequencing (NGS) enables not only the evaluation of established HCM genes but also candidate genes for cardiomyopathy.

The Junctophilin-2 gene (JPH2) is the major structural protein in cardiomyocytes for coupling of transverse (T) tubule-associated L-type Ca2+ channels and type-2 ryanodine receptors on the sarcoplasmic reticulum within junctional membrane complexes (JMC). Downregulation of the JPH2 gene has been associated with heart failure and variants in this gene have been suggested to associate with HCM. The role of the JPH2 gene in cardiomyopathies has been obscure as only one rare variant segregating with any type of cardiomyopathy has been published (Sabater-Molina M et al., Clin Genet. 2016). This study characterizes the cardiac phenotype related to JPH2 c.482C>A, p.(Thr161Lys) variant in nine Finnish index patients and their family members.

Keywords: hypertrophic cardiomyopathy, Junctophilin-2 gene, oligonucleotide-selective sequencing, founder mutation

Authors: Sari U.M. Vanninen, Krista Leivo, Eija H. Seppälä, Julie Hathaway, Tiia Maria Luukkonen, Katriina Aalto-Setälä, Olli Pitkänen, Piia Suursalmi, Antti-Pekka Annala, Ismo Anttila, Tero-Pekka Alastalo, Samuel Myllykangas, Tiina Heliö, Juha W. Koskenvuo


Last modified: December 12, 2018