{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:35:06Z","timestamp":1765344906169,"version":"3.46.0"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministry of Health of Italy","doi-asserted-by":"crossref","award":["T3-AN-04"],"award-info":[{"award-number":["T3-AN-04"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Cardiomyopathies are a heterogeneous group of heart muscle disorders with diverse genetic origins. Biallelic loss-of-function (LoF) variants in the nebulin-related anchoring protein (NRAP) gene have been linked to dilated cardiomyopathy (DCM) and left ventricular noncompaction cardiomyopathy, though only a few families have been described. NRAP, a member of the Nebulin family, plays a key role in cardiomyocyte development, structural integrity, and muscle function. Methods: We investigated two Italian siblings with DCM born to consanguineous parents from a small village in Campania. Exome sequencing, homozygosity mapping, and comparative analyses with other reported cases were performed. Genealogical research was conducted using civil registry data to reconstruct extended family pedigrees. Results: Both siblings were homozygous for a LoF variant in NRAP (NM_198060.4:c.619del; p.Val207TrpfsTer20). A third brother with tachycardia-induced cardiomyopathy, as well as their living mother, who did not have cardiac abnormalities, were found to be heterozygous. The same homozygous variant was recently identified in another Italian family with DCM coming from North-eastern Italy, whose proband also originated from a nearby village in Campania. These two families exhibited heterogeneity in clinical presentation. Homozygosity analysis revealed a &gt;25 Mb shared region on chromosome 10 encompassing NRAP, supporting a common ancestral origin. While genealogical reconstruction did not allow identification of a shared ancestor, it confirmed consanguinity and enabled the recognition of potential carriers across both families. Conclusions: Our findings strengthen the evidence for NRAP as a disease-causing gene in cardiomyopathies and highlight a likely founder effect in Campania. Incorporating NRAP into genetic testing panels is warranted, especially in populations with high rates of consanguinity or suspected founder variants.<\/jats:p>","DOI":"10.3390\/genes16121470","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"1470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Common Ancestry from Southern Italy: Two Families with Dilated Cardiomyopathy Share the Same Homozygous Loss-of-Function Variant in NRAP"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8329-0215","authenticated-orcid":false,"given":"Maria Elena","family":"Onore","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3805-4170","authenticated-orcid":false,"given":"Martina","family":"Caiazza","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases Unit, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6245-8266","authenticated-orcid":false,"given":"Catia","family":"Mio","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED), University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-0711","authenticated-orcid":false,"given":"Gioacchino","family":"Scarano","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases Unit, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"},{"name":"U.O.S.D. Genetica Medica, A.O.R.N. San Pio, 82100 Benevento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0214-8004","authenticated-orcid":false,"given":"Pasquale","family":"Di Letto","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Iffat","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Monda","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases Unit, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7949-7771","authenticated-orcid":false,"given":"Cristiano","family":"Amarelli","sequence":"additional","affiliation":[{"name":"Unit of Innovative Procedures in General Cardiac Surgery and Transplantation, Department of Cardiac Surgery, A.O.R.N. Ospedale dei Colli, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella Nicoletta","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1483-3612","authenticated-orcid":false,"given":"Flavio","family":"Faletra","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED), University of Udine, 33100 Udine, Italy"},{"name":"Institute of Medical Genetics, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Nigro","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM), 80078 Pozzuoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8291-9517","authenticated-orcid":false,"given":"Giuseppe","family":"Limongelli","sequence":"additional","affiliation":[{"name":"Inherited and Rare Cardiovascular Diseases Unit, Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Institute of Cardiovascular Science, University College, London WC1E 6BT, UK"},{"name":"St. Bartholomew\u2019s Hospital, London EC1A 7BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-125X","authenticated-orcid":false,"given":"Giulio","family":"Piluso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1093\/eurheartj\/ehad194","article-title":"2023 ESC Guidelines for the management of cardiomyopathies","volume":"44","author":"Arbelo","year":"2023","journal-title":"Eur. 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