筋ジストロフィー関連遺伝子SGCBが重症拡張型心筋症の原因でもあることを発見 ～東アジア人に多いSGCBの遺伝子変化を世界で初めて解明、将来の治療法開発へ前進～

2026-06-30 国立循環器病研究センター,大阪大学

図：SGCB遺伝子の変化による拡張型心筋症発症の仕組み

＜関連情報＞

• https://www.ncvc.go.jp/pr/release/pr_53169/
• https://www.jci.org/articles/view/198675

ホモ接合型SGCBスプライス部位変異は、東アジア人においてサルコグリカン複合体の不安定化を介して孤立性拡張型心筋症を引き起こす Homozygous SGCB splice-site variant causes isolated dilated cardiomyopathy through sarcoglycan complex destabilization in East Asians

Fangfang Li, Haruki Shinomiya, Yuki Kuramoto, Koshiro Kanaoka, Yuji Sakahashi, Yasuki Ishihara, Hidetaka Kioka, Seiko Ide, Yumi Yamaguchi-Kabata, Shu Tadaka, Ikuko N. Motoike, Kengo Kinoshita, Kinuko Ohneda,^, Hidetoshi Sakurai, Takahiro Okumura, Yohei Miyashita, Kota Jojima, Hisakazu Kato, Ken Matsuoka, Kazuya Tanabe, Shunsuke Nishimura, Seiji Takashima, Yoshihiro Asano, and Yasushi Sakata
The Journal of Clinical Investigation  Published June 1, 2026
DOI:https://doi.org/10.1172/JCI198675

Abstract

Dilated cardiomyopathy (DCM) is a genetically heterogeneous disorder, characterized by ventricular dilatation and impaired systolic function, leading to heart failure and sudden cardiac death. Despite advances in genomic technologies, the genetic cause of DCM remains unidentified in more than half of the cases. Here, we performed an integrative analysis of genomic and transcriptomic data from patient-derived cardiac tissue to identify causative variants in genetically undiagnosed DCM. This approach enabled us to identify a homozygous splice-site variant (c.243+6T>A) in the sarcoglycan gene SGCB, which results in exon 2 skipping. This variant was significantly enriched in patients with DCM compared with the general population, with consistent genotype–phenotype correlations observed across multiple families. Protein-level analysis of cardiac tissue from homozygous individuals revealed loss of β-sarcoglycan, the protein product of SGCB, and destabilization of the sarcoglycan complex. Although SGCB has been previously associated with limb-girdle muscular dystrophy, these homozygous individuals showed no biochemical or clinical signs of skeletal muscle involvement, indicating an absence of myopathy. Compared with variant-negative patients with DCM, homozygous individuals also had a higher risk of early-onset adverse cardiac events. Together, these findings identify c.243+6T>A in SGCB as a cause of isolated DCM associated with unfavorable clinical outcomes.