A novel homozygous missense mutation in PNPLA2 in a patient manifesting primary triglyceride deposit cardiomyovasculopathy

Yasuhiro Hara; Yoshihiko Ikeda; Hayato Kimura; Shinsaku Shimamoto; Mao Ishikawa; Kunihisa Kobayashi; Hironori Nagasaka; Hisashi Shimoyama; Ken-Ichi Hirano

doi:10.1016/j.ymgmr.2023.100960

A novel homozygous missense mutation in PNPLA2 in a patient manifesting primary triglyceride deposit cardiomyovasculopathy

Mol Genet Metab Rep. 2023 Feb 10:34:100960. doi: 10.1016/j.ymgmr.2023.100960. eCollection 2023 Mar.

Authors

Yasuhiro Hara¹, Yoshihiko Ikeda^{1

2}, Hayato Kimura³, Shinsaku Shimamoto⁴, Mao Ishikawa¹, Kunihisa Kobayashi⁵, Hironori Nagasaka⁶, Hisashi Shimoyama⁴, Ken-Ichi Hirano¹

Affiliations

¹ Laboratory of Novel, Non-invasive, and Nutritional Therapeutics (CNT), Department of Triglyceride Science, Graduate School of Medicine, Osaka University, 6-2-4, Furuedai, Suita, Osaka 565-0874, Japan.
² Department of Pathology, National Cerebral and Cardiovascular Center, 6-1, Kishibeshinmachi, Suita, Osaka 564-8565, Japan.
³ Department of Pathology, Itami City Hospital, 1-100, Koyaike, Itami, Hyogo 664-8540, Japan.
⁴ Department of Cardiology, Itami City Hospital, 1-100, Koyaike, Itami, Hyogo 664-8540, Japan.
⁵ Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, 1-1-1, Zokumyoin, Chikushino, Fukuoka 818-8502, Japan.
⁶ Department of Pediatrics, Iwate Prefectural Isawa Hospital, 61, Aza Ryugababa, Mizusawa, Ohshu, Iwate 023-0864, Japan.

Abstract

Primary triglyceride deposit cardiomyovasculopathy (P-TGCV), caused by a rare genetic mutation in PNPLA2 encoding adipose triglyceride lipase (ATGL), exhibits severe cardiomyocyte steatosis and heart failure. Here, we report the case of a 51-year-old man with P-TGCV homozygous for a novel PNPLA2 mutation (c.446C > G, P149R) in the catalytic domain of ATGL. Analyses of endomyocardial biopsy specimens and in vitro expression experiments showed mutant protein expression with conserved lipid binding, but reduced lipolytic activity, indicating mutation pathogenicity.

Keywords: ATGL, adipose triglyceride lipase; Adipose triglyceride lipase; BMIPP, 123I-β-idophenyl-p-pentadecanoic acid; CTx, cardiac transplantation; HE, hematoxylin-eosin; Heart failure; Mutation; NLSD, neutral lipid storage disease; NLSD-I, NLSD with ichthyosis; NLSD-M, NLSD with myopathy; PCR, polymerase chain reaction; PLIN2, perilipin-2; PNPLA2; TGCV, triglyceride deposit cardiomyovasculopathy; Triglyceride deposit cardiomyovasculopathy; WR, washout rate.

Publication types

Case Reports