{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:43Z","timestamp":1753869403177,"version":"3.41.2"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873482","81873483"],"award-info":[{"award-number":["81873482","81873483"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital heart disease (CHD) is a class of cardiovascular defects that includes septal defects, outflow tract abnormalities, and valve defects. Human homolog of Drosophila headcase (<jats:italic>HECA<\/jats:italic>) is a novel cell cycle regulator whose role in CHD has not been elucidated. This is the first study to determine the frequency of <jats:italic>HECA<\/jats:italic> mutations in patients with CHD and the association between <jats:italic>HECA<\/jats:italic> variants and CHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we identified a candidate gene, <jats:italic>HECA<\/jats:italic>, by whole\u2010exome sequencing of an atrial septal defect family. To investigate the association between <jats:italic>HECA<\/jats:italic> variants and CHD risk, targeted exon sequencing was conducted in 689 individuals with sporadic CHD. We further analyzed the effect of <jats:italic>HECA<\/jats:italic> gene abnormalities on cardiomyocyte phenotype behavior and related signaling pathways by Western blotting, reverse transcription\u2010quantitative polymerase chain reaction, and scratch assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a novel de novo mutation, c.409_410insA (p. W137fs), in the <jats:italic>HECA<\/jats:italic> gene and identified five rare deleterious variants that met the filtering criteria in 689 individuals with sporadic CHD. Fisher's exact test revealed a significant association between <jats:italic>HECA<\/jats:italic> variations and CHD compared with those in gnomADv2\u2010East Asians(<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0027). Further functional analysis suggested that the variant p. W137fs resulted in a deficiency of the normal HECA protein, and HECA deficiency altered AC16 cell cycle progression, increased cell proliferation, and migration, and promoted the activation of the PDGF\u2010BB\/PDGFRB\/AKT pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study identified <jats:italic>HECA<\/jats:italic> and its six rare variants, expanding the spectrum of genes associated with CHD pathogenesis in the Chinese population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24649","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T03:39:55Z","timestamp":1660189195000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional analysis of <i>HECA<\/i> variants identified in congenital heart disease in the Chinese population"],"prefix":"10.1002","volume":"36","author":[{"given":"Ting","family":"Li","sequence":"first","affiliation":[{"name":"Children's Hospital of Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Birth Defects  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Wu","sequence":"additional","affiliation":[{"name":"Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Children's Hospital of Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Birth Defects  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Xue","sequence":"additional","affiliation":[{"name":"Children's Hospital of Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Birth Defects  Shanghai 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