{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:55:55Z","timestamp":1753869355700,"version":"3.41.2"},"reference-count":19,"publisher":"Wiley","issue":"21-22","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201553"],"award-info":[{"award-number":["82201553"]}],"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":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>An accurate genetic diagnosis of Becker muscular dystrophy (BMD) can be sometimes challenging due to deep intronic <jats:italic>DMD<\/jats:italic> variants. Here, we report on the genetic diagnosis of a BMD patient with a novel deep\u2010intronic splice\u2010altering variant in <jats:italic>DMD<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The index case was a 3.8\u2010year\u2010old boy who was suspected of having a diagnosis of BMD based on his clinical, muscle imaging, and pathological features. Routine genomic detection approaches did not detect any disease\u2010causing variants in him. Muscle\u2010derived <jats:italic>DMD<\/jats:italic> mRNA studies, followed by genomic Sanger sequencing and <jats:italic>in silico<\/jats:italic> bioinformatic analyses, were performed in the patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>DMD<\/jats:italic> mRNA studies detected a cryptic exon\u2010containing transcript and normally spliced <jats:italic>DMD<\/jats:italic> transcript in the patient. The cryptic exon\u2010containing transcript encoded a frameshift and premature termination codon (NP_003997.1:p.[=,Asp2740Valfs*52]). Further genomic Sanger sequencing and bioinformatic analysis identified a novel deep\u2010intronic splice\u2010altering variant in <jats:italic>DMD<\/jats:italic> (c.8217\u2009+\u200923338A\u2009&gt;\u2009G). The novel variant strengthened a cryptic donor splice site and activated a cryptic acceptor splice site in the deep\u2010intronic region of <jats:italic>DMD<\/jats:italic> intron 55, resulting in the activation of a new <jats:italic>dystrophin<\/jats:italic> cryptic exon found in the patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our case report expands the genetic spectrum of BMD and highlights the essential role of deep\u2010intronic cryptic exon\u2010activating variants in genetically unsolved BMD patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24987","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T04:58:10Z","timestamp":1700110690000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cryptic exon activation caused by a novel deep\u2010intronic splice\u2010altering variant in Becker muscular dystrophy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-6026","authenticated-orcid":false,"given":"Zhiying","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengyue","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University People's Hospital  Beijing 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"GrandOmics Biosciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Liang","sequence":"additional","affiliation":[{"name":"GrandOmics Biosciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianbo","family":"Luo","sequence":"additional","affiliation":[{"name":"GrandOmics Biosciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingchao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University First Hospital  Beijing 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