{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:28:29Z","timestamp":1773289709416,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Syndromic dilated cardiomyopathy (DCM) includes a group of complex disorders with a very heterogeneous genetic etiology, leading to\u00a0delay\u00a0in\u00a0definitive diagnosis.\u00a0Conversely, an early genetic diagnosis is very important in determining the disease course, the prognosis, and may guide personalized treatments and family counseling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed two brothers with a multisystemic disorder, including dilated cardiomyopathy, diabetes, bilateral neurosensorial hearing loss, and optic atrophy, using different genetic approaches, namely mitochondrial DNA sequencing, comparative genomic hybridization\u2010array (a\u2010CGH) and whole exome sequencing (WES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequencing of the wide mitochondrial genome revealed, in both brothers, the known homoplasmic variant rs2853826 in the subunit 3 of the <jats:italic>NADH dehydrogenase<\/jats:italic> gene (<jats:italic>MT\u2010ND3<\/jats:italic>), whose pathogenicity was conflicting. Comparative genomic hybridization\u2010array analysis revealed in both patients and their father two heterozygous deletions in Phosphodiesterase 4d\u2010Interacting Protein (<jats:italic>PDE4DIP<\/jats:italic>) and Protocadherin\u2010related 15 (<jats:italic>PCDH15)<\/jats:italic> genes, respectively. The use of WES detected a pathogenetic mutation in <jats:italic>ALMS1<\/jats:italic>, enabling the definitive diagnosis of Alstr\u00f6m syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated how the diagnosis of a complex heterogeneous disease may be difficult, due to several overlapping manifestations and the possible interaction of more genetic variants that could lead to a more severe and complex phenotype.<\/jats:p><jats:p>This paper strongly evidences how genomics is revolutionizing the diagnosis of rare complex disease, representing one of the most essential steps to enable a definitive diagnosis and to establish the etiology for diseases, such as syndromic DCM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1260","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T18:00:05Z","timestamp":1589306405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Genetic analysis resolves differential diagnosis of a familial syndromic dilated cardiomyopathy: A new case of Alstr\u00f6m syndrome"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-1043","authenticated-orcid":false,"given":"Barbara","family":"Lombardo","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples \u201cFederico II\u201d Naples Italy"},{"name":"CEINGE Advanced Biotechnologies Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"D'Argenio","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical 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