{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:26:05Z","timestamp":1760955965991,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20171369","BK20180376"],"award-info":[{"award-number":["BK20171369","BK20180376"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Danon disease (DD) is an X\u2010linked dominant multisystem disorder that is associated with cardiomyopathy, skeletal myopathy, and varying degrees of intellectual disability. It results from mutations in the lysosome\u2010associated membrane protein 2 (<jats:italic>LAMP2<\/jats:italic>) gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Herein, a proband with a mild DD case presenting with a familial hypertrophic cardiomyopathy (HCM) phenotype and additional family members were evaluated. Exome sequencing and Sanger sequencing were performed to explore the genetic basis of DD in the proband. Segregation, in silico, and functional analyses were carried out to explore potential pathogenicity in the candidate mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exome sequencing and Sanger sequencing identified one novel missense mutation (p.G93R) in the <jats:italic>LAMP2<\/jats:italic> gene in the proband, and this mutation was also identified in three other family members. In silico analysis of <jats:italic>LAMP2<\/jats:italic> predicted that the mutation causes a conformational change and subsequent protein destabilization. Furthermore, functional examination showed that mutation carriers have a significant reduction in <jats:italic>LAMP2<\/jats:italic> expression, which supports that the mutation is pathogenic. Moreover, skewed X chromosome inactivation (XCI) was identified in one female mutation carrier, thus suggesting that skewed XCI may be the reason why this individual escaped the pathogenic influence of the mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings will aid in diagnosing DD patients carrying this <jats:italic>LAMP2<\/jats:italic> mutation that presents with a HCM phenotype. Furthermore, this study illustrates the importance of utilizing a molecular diagnostic approach in HCM patients and is the first study to report a <jats:italic>LAMP2<\/jats:italic> p.G93R mutation associated with mild DD and identify that XCI serves a protective role in DD etiology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.941","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T02:43:48Z","timestamp":1567046628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A novel <i>LAMP2<\/i> p.G93R mutation associated with mild Danon disease presenting with familial hypertrophic cardiomyopathy"],"prefix":"10.1002","volume":"7","author":[{"given":"Jing","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, ZhongDa Hospital Southeast University Nanjing P. R. China"},{"name":"Institute of Life Science Southeast University Nanjing P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Life Science Southeast University Nanjing P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Life Science Southeast University Nanjing P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2159-4157","authenticated-orcid":false,"given":"Qiming","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, ZhongDa Hospital Southeast University Nanjing P. R. 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