{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:28:13Z","timestamp":1794360493302,"version":"4.9.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:italic>DMD<\/jats:italic> gene pathogenic variations cause a spectrum of phenotypes, ranging from severe Duchenne muscular dystrophy, the Becker milder cases, the intermediate or very mild muscle phenotypes invariably characterized by high CK, and the ultrarare fully-asymptomatic cases. Besides these phenotypes, X-linked dilated cardiomyopathy is also caused by <jats:italic>DMD<\/jats:italic> mutations. Males carrying <jats:italic>DMD<\/jats:italic> deletions with absent or very mild phenotypes have been sparsely described. We performed a horizon scan on public datasets to enroll males with the above phenotypes and carrying <jats:italic>DMD<\/jats:italic> deletions to delineate myopathic genotype-phenotype relationships. We inventoried 81 males, who were divided into the following clinical categorization: fully-asymptomatic males aged &amp;gt;43 years (A, <jats:italic>N<\/jats:italic> = 22); isolated hyperCKemia (CK, <jats:italic>N<\/jats:italic> = 35); and mild weakness (any age) with or without high CK (WCK, <jats:italic>N<\/jats:italic> = 24). In all cases, deleted intervals were exons 2 to 55, and no downstream exons were ever involved, apart from an exon 78 deletion in a WCK patient. All deletions were in-frame apart from the known exception to the rule of exon 2 and exon 78. We correlated the mild phenotypes (A and CK) to deleted exons, intronic breakpoints, exon-exon junctions, 3\u2032 isoforms rule, and protein epitopes, and we found that some genetic profiles are exclusively\/mainly occurring in A\/CK phenotypes, suggesting they are compatible with a <jats:italic>quasi<\/jats:italic>-normal muscular performance. We discussed diverse pathogenic mechanisms that may contribute to mild dystrophinopathic phenotypes, and we tried to address some \u201ccritical\u201d genetic configurations or exon content needed to preserve a semi-functional <jats:italic>DMD<\/jats:italic> gene.<\/jats:p>","DOI":"10.3389\/fneur.2023.1288721","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:13:23Z","timestamp":1705292003000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["DMD deletions underlining mild dystrophinopathies: literature review highlights phenotype-related mutation clusters and provides insights about genetic mechanisms and 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