Four different CACNA1S missense mutations were detected in hypokalemic periodic paralysis and five KCNJ2 missense mutations in Andersen-Tawil syndrome.
TRPM4 enlarges the subgroup of LQT genes (KCNJ2 in Andersen syndrome and CACNA1C in Timothy syndrome) known to increase the QT interval through a more complex pleiotropic effect than merely action potential alteration.
We performed genetic analysis of KCNJ2 in 32 ATS probands and their family members and identified KCNJ2 mutations in 25 probands, 20 families who underwent extensive genetic testing.
Andersen-Tawil syndrome is caused in a majority of cases by mutations in KCNJ2, which encodes the Kir2.1 subunit of the inwardly rectifying potassium channel.
We report the first patient diagnosed with ATS with a de novo c.G899C mutation in the KCNJ2 gene in 2010 who developed an autoimmune hyperthyroidism and TPP in 2013.
Our aim was to describe the clinical course of ATS in a family, in which the proband survived aborted cardiac arrest (ACA) and genetic screening revealed a previously unknown mutation (c.271_282del12[p.Ala91_Leu94del]) in the KCNJ2 gene.
The loss-of-function mutations in KCNJ2 in ATS1 affect the excitability of both skeletal and cardiac muscle, which underlies the cardiac arrhythmias and periodic paralysis associated with ATS.
In the whole sample (665 patients), 15 out of 104 different CLCN1 mutations accounted for 60% of all patients with myotonia congenita, 11 out of 22 SCN4A mutations for 86% of paramyotonia congenita/sodium channel myotonia pedigrees, and 3 out of 17 KCNJ2 mutations for 42% of ATS pedigrees.
Loss of function mutations of KCNJ2 encoding Kir2.1 result in Andersen-Tawil syndrome, a disorder characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features.