Journal article

Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants

Johanna C Herkert, Judith MA Verhagen, Raquel Yotti, Alireza Haghighi, Dean G Phelan, Paul A James, Natasha J Brown, Chloe Stutterd, Ivan Macciocca, Kai'En Leong, Marian LC Bulthuis, Yolande van Bever, Marjon A van Slegtenhorst, Ludolf G Boven, Amy E Roberts, Radhika Agarwal, Jonathan Seidman, Neal K Lakdawala, Francisco Fernandez-Aviles, Michael A Burke Show all

American Heart Journal | MOSBY-ELSEVIER | Published : 2020

Abstract

INTRODUCTION: Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined. METHODS AND RESULTS: We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense variants, and one homozygous deleterious missense variant were identified. Among 18 live-born patients, 8 exhibited neonatal dilated cardiomyopathy (44.4%; 95% CI: 21.5%-69.2%) that subsequently transitioned into ventricular hypertrophy. The majority of patients had extr..

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