biostudies-literatureUnknown13(4)Murdocca MMandibular hypoplasia, Deafness and Progeroid features with concomitant Lipodystrophy define a rare systemic disorder, named MDPL Syndrome, due to almost always a <i>de novo</i> variant in <i>POLD1</i> gene, encoding the DNA polymerase δ. We report a MDPL female heterozygote for the recurrent p.Ser605del variant. In order to deepen the functional role of the in frame deletion affecting the polymerase catalytic site of the protein, cellular phenotype has been characterised. MDPL fibroblasts exhibit <i>in vitro</i> nuclear envelope anomalies, accumulation of prelamin A and presence of micronuclei. A decline of cell growth, cellular senescence and a blockage of proliferation in G0/G1 phase complete the aged cellular picture. The evaluation of the genomic instability reveals a delayed recoveryAging4926-4945https://www.ebi.ac.uk/biostudies/studies/S-EPMC7950258biostudies-literatureFunctional analysis of <i>POLD1</i> p.ser605del variant: the aging phenotype of MDPL syndrome is associated with an impaired DNA repair capacity.PMC7950258Marinaccio JMurdocca MUdroiu ISanchez MFiorillo CD'Apice MRDe Masi CD'Adamo MTalarico RVNovelli GSpitalieri PSangiuolo FSbraccia PSgura AfalseFunctional analysis of <i>POLD1</i> p.ser605del variant: the aging phenotype of MDPL syndrome is associated with an impaired DNA repair capacity.Mandibular hypoplasia, Deafness and Progeroid features with concomitant Lipodystrophy define a rare systemic disorder, named MDPL Syndrome, due to almost always a <i>de novo</i> variant in <i>POLD1</i> gene, encoding the DNA polymerase δ. We report a MDPL female heterozygote for the recurrent p.Ser605del variant. In order to deepen the functional role of the in frame deletion affecting the polymerase catalytic site of the protein, cellular phenotype has been characterised. MDPL fibroblasts exhibit <i>in vitro</i> nuclear envelope anomalies, accumulation of prelamin A and presence of micronuclei. A decline of cell growth, cellular senescence and a blockage of proliferation in G0/G1 phase complete the aged cellular picture. The evaluation of the genomic instability reveals a delayed recovery2021-01-01T00:00:00Z2021 Feb2026-05-08T16:13:18.093Z2025-04-19T18:01:20.719ZS-EPMC79502583361833310.18632/aging.202680