A novel KCNH2 frameshift mutation (c.46delG) associated with high risk of sudden death in a family with congenital long QT syndrome type 2

摘要: The congenital long QT syndrome type 2 is caused by mutations in KCNH2 gene that encodes the alpha subunit of potassium channel Kv11.1. carriers pathogenic variant manifest a phenotype characterized prolongation interval and increased risk sudden cardiac death due to life-threatening ventricular tachyarrhythmias. A family composed 17 members with history recurrent syncopes was studied. DNA proband clinical manifestations analyzed using massive sequencer included following genes: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, ANK2, KCNJ2, CACNA1, CAV3, SCN1B, SCN4B, AKAP9, SNTA1, CALM1, KCNJ5, RYR2 TRDN. sequencing identified novel produced heterozygous frameshift mutation c.46delG, pAsp16Thrfs*44 resulting synthesis truncated Kv11.1 ion channel. Eight manifested syndrome. study segregation Sanger revealed identical several positive phenotype. genetic findings this demonstrate causing haploinsufficiency can result severe phenotypic manifestation an elevated death.