ウト　ケンタ   Uto Kenta   宇都　健太    所属   医学部 医学科（東京女子医科大学病院）    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Identification of MYLK3 mutations in familial dilated cardiomyopathy.
掲載誌名	正式名：Scientific reports 略　 称：Sci Rep ISSNコード：2045-2322
掲載区分	国外
出版社	Nature Research
巻・号・頁	7(1),pp.17495
著者・共著者	Tobita Takashige†, Nomura Seitaro, Morita Hiroyuki, Ko Toshiyuki, Fujita Takanori, Toko Haruhiro, Uto Kenta, Hagiwara Nobuhisa, Aburatani Hiroyuki*, Komuro Issei*
発行年月	2017/12
概要	Dilated cardiomyopathy (DCM) is a primary cause of heart failure, life-threatening arrhythmias, and cardiac death. Pathogenic mutations have been identified at the loci of more than 50 genes in approximately 50% of DCM cases, while the etiologies of the remainder have yet to be determined. In this study, we applied whole exome sequencing in combination with segregation analysis to one pedigree with familial DCM, and identified a read-through mutation (c.2459 A > C; p.*820Sext*19) in the myosin light chain kinase 3 gene (MYLK3). We then conducted MYLK3 gene screening of 15 DCM patients (7 familial and 8 sporadic) who were negative for mutation screening of the previously-reported cardiomyopathy-causing genes, and identified another case with a MYLK3 frameshift mutation (c.1879_1885del; p.L627fs*41). In vitro experiments and immunohistochemistry suggested that the MYLK3 mutations identified in this study result in markedly reduced levels of protein expression and myosin light chain 2 phosphorylation. This is the first report that MYLK3 mutations can cause DCM in humans. The clinical phenotypes of DCM patients were consistent with MYLK3 loss-of-function mouse and zebrafish models in which cardiac enlargement and heart failure are observed. Our findings highlight an essential role for cardiac myosin light chain kinase in the human heart.
DOI	10.1038/s41598-017-17769-1
PMID	29235529