High prevalence of ALPK3 premature terminating variants in Korean hypertrophic cardiomyopathy patients

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Authors: Seung Woo Ryu ; Won Chan Jeong ; Geu Ru Hong ; Jung Sun Cho ; Soo Yong Lee ; Hyungseop Kim ; Jeong Yoon Jang ; Sun Hwa Lee ; Dae-Hwan Bae ; Jae Yeong Cho ; Ji Hee Kim ; Kyung-Hee Kim ; Jang Won Son ; Beomman Han ; Go Hun Seo ; Hane Lee

Keywords: ALPK3 ; Korean HCMP population ; hypertrophic cardiomyopathy ; premature terminating variant ; whole exome sequencing

Abstract: Background: The alpha-protein kinase 3 (ALPK3) gene (OMIM: 617608) is associated with autosomal recessive familial hypertrophic cardiomyopathy-27 (CMH27, OMIM: 618052). Recently, several studies have shown that monoallelic premature terminating variants (PTVs) in ALPK3 are associated with adult-onset autosomal dominant hypertrophic cardiomyopathy (HCMP). However, these studies were performed on patient cohorts mainly from European Caucasian backgrounds.

Methods: To determine if this finding is replicated in the Korean HCMP cohort, we evaluated 2,366 Korean patients with non-syndromic HCMP using exome sequencing and compared the cohort dataset with three independent population databases.

Results: We observed that monoallelic PTVs in ALPK3 were also significantly enriched in Korean patients with HCMP with an odds ratio score of 10-21.

Conclusions: We suggest that ALPK3 PTV carriers be considered a risk group for developing HCMP and be monitored for cardiomyopathies.