{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:25:14Z","timestamp":1777551914529,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>\n                    Mandibular hypoplasia, deafness, and progeroid features, with concomitant lipodystrophy, define a multisystem disorder named MDPL syndrome. MDPL has been associated with heterozygous mutations in\n                    <jats:italic toggle=\"yes\">POLD1<\/jats:italic>\n                    gene resulting in loss of DNA polymerase \u03b4 activity. In this study, we report clinical, genetic, and cellular studies of a 13-year-old Pakistani girl, presenting growth retardation, sensorineural deafness, altered distribution of subcutaneous adipose tissue, and insulin resistance. We performed Sanger sequencing of\n                    <jats:italic toggle=\"yes\">POLD1<\/jats:italic>\n                    gene in the proband and the healthy parents. Fibroblasts obtained from dermal biopsy were evaluated for the specific hallmarks of cellular senescence and for their response to the DNA-induced damage. Patient carried the recurrent heterozygous\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    in frame deletion (c.1812_1814delCTC,\n                    <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/p.Ser605del\">p.Ser605del<\/jats:uri>\n                    ) within\n                    <jats:italic toggle=\"yes\">POLD1<\/jats:italic>\n                    gene, previously detected in 16 MDPL patients. In patient's fibroblasts we observed severe nuclear envelope anomalies, presence of micronuclei, accumulation of prelamin A, altered cell growth, and cellular senescence. In addition, we observed a persistence of DNA damage after cisplatin exposure, compared to control cells. In conclusion, the MDPL nuclear and cellular findings resemble features observed in other progeroid syndromes and familial lipodystrophies. Although further investigations will be necessary, these information could be used to establish targeted therapeutic approaches.\n                  <\/jats:p>","DOI":"10.1089\/dna.2018.4335","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T15:59:15Z","timestamp":1541174355000},"page":"1061-1067","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Characterization of MDPL Fibroblasts Carrying the Recurrent p.Ser605del Mutation in\n                    <i>POLD1<\/i>\n                    Gene"],"prefix":"10.1177","volume":"37","author":[{"given":"Chiara","family":"Fiorillo","sequence":"first","affiliation":[{"name":"Paediatric Neurology and Neuromuscular Disorders, University of Genoa and Istituto G. Gaslini, Genoa, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosaria","family":"D'Apice","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Tor Vergata Hospital, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Trucco","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Neuromuscular Disorders, University of Genoa and Istituto G. Gaslini, Genoa, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Murdocca","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata,\u201d Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Spitalieri","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata,\u201d Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Assereto","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Neuromuscular Disorders, University of Genoa and Istituto G. Gaslini, Genoa, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Baratto","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Neuromuscular Disorders, University of Genoa and Istituto G. Gaslini, Genoa, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Morcaldi","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Neuromuscular Disorders, University of Genoa and Istituto G. Gaslini, Genoa, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Minetti","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Neuromuscular Disorders, University of Genoa and Istituto G. Gaslini, Genoa, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Sangiuolo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Tor Vergata Hospital, Rome, Italy."},{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata,\u201d Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Tor Vergata Hospital, Rome, Italy."},{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata,\u201d Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,12,5]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2005.10.011"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg213"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13311"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.08.052"},{"key":"e_1_3_3_6_1","first-page":"3876","article-title":"Short stature as the first manifestation of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome","volume":"10","author":"Chen T.","year":"2017","unstructured":"Chen T., , Li M., , Wu H., , Xie R., , Wang F., , Chen X., et al. (2017). Short stature as the first manifestation of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome. 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