Hirono Keiichi, Hata Yukiko, Ichimata Shojiro, Nishida Naoki, Imamura Teruhiko, Asano Yoshihiro, Kuramoto Yuki, Tsuboi Kaori, Takarada Shinya, Okabe Mako, Nakaoka Hideyuki, Ibuki Keijiro, Ozawa Sayaka, Muneuchi Jun, Yasuda Kazushi, Urayama Kotaro, Oka Hideharu, Miyamoto Tomoyuki, Baba Kenji, Kato Akio, Saiki Hirofumi, Kuwabara Naoki, Harada Masako, Baba Shiro, Morikawa Mari, Iwasaki Hidenori, Hirata Yuichiro, Ito Yuki, Sakaguchi Heima, Urata Susumu, Toda Koichi, Kittaka Emi, Okada Seigo, Hasebe Yohei, Hoshino Shinsuke, Fujii Takanari, Mitsushita Norie, Nii Masaki, Ogino Kayo, Fujino Mitsuhiro, Yoshida Yoko, Fukuda Yutaka, Iwashima Satoru, Takigiku Kiyohiro, Sakata Yasushi, Inuzuka Ryo, Maeda Jun, Hayabuchi Yasunobu, Fujioka Tao, Namiki Hidemasa, Fujita Shuhei, Nishida Koichi, Kuraoka Ayako, Kan Nobuhiko, Kido Sachiko, Watanabe Ken, Ichida Fukiko
Department of Pediatrics, Faculty of Medicine, University of Toyama, Toyama City, 2630 Sugitani, Toyama, 930-0194, Japan.
Legal Medicine, University of Toyama, Toyama, Japan.
Sci Rep. 2024 Dec 16;14(1):30469. doi: 10.1038/s41598-024-77360-3.
Dilated cardiomyopathy (DCM) is a progressive myocardial disorder characterized by impaired cardiac contraction and ventricular dilation. However, some patients with DCM improve when experiencing left ventricular reverse remodeling (LVRR). Currently, the detailed association between genotypes and clinical outcomes, including LVRR, particularly among children, remains uncertain. Pediatric patients with DCM from multiple Japanese institutions recorded between 2014 and 2023 were enrolled. We identified their DCM-related genes and explored the association between gene variants and clinical outcomes, including LVRR. We included 123 pediatric patients (62 males; median age: 8 [1-51] months) and found 50 pathogenic variants in 45 (35.0%) of them. The most identified gene was MYH7 (14.0%), followed by RYR2 (12.0%) and TPM1 (8.0%). LVRR was achieved in 47.5% of these patients. The left ventricular ejection fraction remained unchanged (31.4% to 39.8%, P = 0.1913) in patients with sarcomere gene variants and in those with non-sarcomere gene variants (33.4% to 47.8%, P = 0.0522) but significantly increased in those without gene variants (33.6% to 54.1%, P < 0.0001). LVRR was not uniform across functional gene groups. Hence, an individualized gene-guided prediction approach may be adopted for children with DCM.
扩张型心肌病（DCM）是一种进行性心肌疾病，其特征为心脏收缩功能受损和心室扩张。然而，一些DCM患者在经历左心室逆向重构（LVRR）时病情会有所改善。目前，基因型与临床结局（包括LVRR）之间的详细关联，尤其是在儿童中，仍不明确。纳入了2014年至2023年间来自多个日本机构的DCM儿科患者。我们确定了他们的DCM相关基因，并探讨了基因变异与临床结局（包括LVRR）之间的关联。我们纳入了123名儿科患者（62名男性；中位年龄：8[1-51]个月），其中45名（35.0%）发现了50个致病变异。最常鉴定出的基因是MYH7（14.0%），其次是RYR2（12.0%）和TPM1（8.0%）。这些患者中有47.5%实现了LVRR。肌节基因变异患者和非肌节基因变异患者的左心室射血分数保持不变（分别从31.4%至39.8%，P = 0.1913；从33.4%至47.8%，P = 0.0522），但无基因变异患者的左心室射血分数显著增加（从33.6%至54.1%，P < 0.0001）。LVRR在各功能基因组中并不一致。因此，对于DCM儿童患者，可采用个体化的基因导向预测方法。
