Abstract
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. 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. Our two patients expand the phenotypic spectrum associated with the c.1159G > C KCNJ5 variant, though...Continue Reading
References
Jun 26, 2003·Nucleic Acids Research·Pauline C Ng, Steven Henikoff
Oct 1, 2005·Brain : a Journal of Neurology·S L VenanceUNKNOWN CINCH investigators
Mar 31, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·James C Cleland, Eric L Logigian
Feb 12, 2009·Heart, Lung & Circulation·Chuan ZhangFan-Ping Wei
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 22, 2010·American Journal of Human Genetics·Yanzong YangYi-Han Chen
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Dec 28, 2010·Journal of the American College of Cardiology·Ilan GoldenbergLi Zhang
Jun 12, 2013·The Journal of Physiology·Ahmad S AminArthur A M Wilde
Jul 4, 2013·Human Genetics·David N CooperHildegard Kehrer-Sawatzki
Feb 4, 2014·Nature Genetics·Martin KircherJay Shendure
Feb 28, 2014·Neurology·Yosuke KokunaiMasanori P Takahashi
Aug 5, 2014·Neuromuscular Disorders : NMD·A FurbyB Fontaine
Jun 26, 2015·Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc·Michalina JagodzińskaElżbieta Katarzyna Biernacka
Feb 26, 2016·Journal of Human Genetics·Koichiro HigasaFumihiko Matsuda
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Sep 23, 2016·Journal of the Neurological Sciences·Hideki KatoShigehisa Mitake
Dec 17, 2017·Circulation. Cardiovascular Genetics·Ying LinYingying Tang
Jun 27, 2019·Human Genome Variation·Shu TadakaKengo Kinoshita
Aug 28, 2020·BMJ Case Reports·Margarita E PolyakElena Zaklyazminskaya