A Preventable Congenital Heart Malformation Syndrome Caused by a Mutation in the Glycolytic Gene PFKP

JACC Basic to Translational Science 2026 Open access

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Authors: Siyao Zhang, Hairui Sun, Ze Xu, Xiaoyan Hao, Jiaqi Fan, Hongmei Xia, R. Liu, Taoyan Liu, Pengyun Gong, Yi Tong, Ye Zhang, Xiaoyan Gu
+8 more Jiancheng Han, Xiaowei Li, Hankui Liu, LiYing Yan, Feng Lan, Hongjia Zhang, Jie Qiao, Yihua He
DOI: 10.1016/j.jacbts.2026.101599
Cited by: 1
References: 26

Abstract

This study reports a congenital heart disease, characterized by ventricular wall thinning and septal defects, caused by a heterozygous missense mutation (R755 W) in the glycolytic gene PFKP (platelet isoform of phosphofructokinase-1). The pathogenic mechanism involves the PFKP mutation impairing enzyme activity, which inhibits cardiomyocyte proliferation and leads to the thinning of the compact myocardium. In the mouse model, we found that administering the downstream metabolite, fructose-1,6-bisphosphate, reversed the myocardial hypoplasia in fetal mice, providing proof-of-concept for in utero intervention. Clinically, we successfully prevented the transmission of the disease using preimplantation genetic testing, resulting in the birth of a healthy infant.

Fields of Study & Subjects

Congenital heart defects research Genomics and Rare Diseases Genetic Syndromes and Imprinting

Publication details

Journal / source
JACC Basic to Translational Science
Publisher
Elsevier BV
Volume
11
Issue
8
Pages
101599–101599
Publication date
1 July 2026
Language
EN