KCNJ5 – Type 13 Long QT Syndrome

Long QT syndrome type 13 (LQT13) is an autosomal dominant cardiac repolarization disorder caused by loss-of-function variants in the inward rectifier potassium channel subunit Kir3.4 encoded by KCNJ5. A single four-generation Han Chinese pedigree carrying the heterozygous c.1159G>C (p.Gly387Arg) variant demonstrated co-segregation of the mutation with prolonged corrected QT and QTpeak intervals in eight carriers across the family ([PMID:23872692]). Electrocardiographic analysis revealed significant prolongation of QTc and QTpeak intervals (P < .01), abnormal T-wave morphology combination scores (P < .01), and reduced low frequency/high frequency heart rate variability ratio (P < .01) compared with matched controls, consistent with a loss of repolarizing current and haploinsufficiency mechanism.

Although functional electrophysiology of the Kir3.4-Gly387Arg channel has not been characterized in heterologous systems, the clinical ECG phenotype in carriers supports impaired channel function. No additional pedigrees or unrelated probands have been reported to date, and there are no refuting studies. Further case series and in vitro assays are required to confirm pathogenicity and support clinical decision-making.

Key take-home: Heterozygous KCNJ5 c.1159G>C (p.Gly387Arg) is associated with LQT13 in a single family, but evidence remains limited and warrants additional validation before routine diagnostic application.

References

• Heart rhythm • 2013 • The phenotype characteristics of type 13 long QT syndrome with mutation in KCNJ5 (Kir3.4-G387R). PMID:23872692

Evidence Based Scoring (AI generated)