Familial periodic paralysis associated with a rare KCNJ5 variant that supposed to have incomplete penetrance

Background: The periodic paralyses are a group of skeletal muscle channelopathies caused by variants in several ion channel genes. Potassium Inwardly Rectifying Channel Subfamily J Member 5 (KCNJ5) encodes the G-protein-activated inwardly rectifying potassium channel 4 (Kir3.4) and the heterozygous KCNJ5 variants cause familial hyperaldosteronism and long QT syndrome (LQTS). Recent studies suggested that variants in KCNJ5 are also causative for Andersen-Tawil syndrome, which showed periodic paralysis and characteristic electrocardiogram features. Clinical report. We found a heterozygous KCNJ5 variant c.1159G > C, p.(Gly387Arg) in an individual with familial periodic paralysis using exome sequencing. Sanger sequencing revealed that this variant was inherited from his affected mother. The same variant had been previously found in two cases of familial LQTS or Andersen-Tawil syndrome, and functional analysis suggested that this variant might have loss of function effect on channel activity. However, the allele frequency of c.1159G > C variant in an East Asian population of public databases ranged from 0.21% to 0.25%, indicating possible incomplete penetrance. Conclusions: Our two patients expand the phenotypic spectrum associated with the c.1159G > C KCNJ5 variant, though the variant has very low penetrance. (c) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Automated summary

Variants in the KCNJ5 gene can cause periodic paralysis and other diseases. These variants are present in the East Asian population but have low penetrance.