{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:33:54Z","timestamp":1790400834646,"version":"4.1.0"},"reference-count":21,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Many proteins are causative for inherited partial lipodystrophies, including lamins, the essential constituents of the nuclear envelope scaffold called the lamina. By performing high throughput sequencing on a panel of genes involved in lipodystrophies, we identified a heterozygous mutation in LMNB2 gene (c.700C &gt; T p.(Arg234Trp)) in a female patient presenting early onset type II diabetes, hypertriglyceridemia, and android fat distribution. This mutation is rare in the general population (frequency 0.013% in GnomAD) and was predicted pathogenic by a set of pathogenicity prediction software. Patient-derived fibroblasts showed nuclear shape abnormalities and premature senescence features, which are two typical cellular phenotypes associated with laminopathies. Moreover, we observed an atypical aggregation of lamin B2 in nucleoplasm, which co-distributes with emerin and lamin A\/C, along with an abnormal distribution of lamin A\/C at the nuclear envelope. Finally, reducing lamin B2 expression level by siRNA targeted toward LMNB2 transcripts resulted in decreased nuclear anomalies and senescence-associated beta-galactosidase, suggesting a role of the mutated protein in the occurrence of the observed cellular phenotype. Altogether, these results suggest that mutations in lamin B2 could produce premature senescence and partial lipodystrophy features as observed with certain mutants of lamin A\/C.<\/jats:p>","DOI":"10.3390\/cells11010050","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"50","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Rare Mutation in LMNB2 Associated with Lipodystrophy Drives Premature Cell Senescence"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1670-4884","authenticated-orcid":false,"given":"Alice-Ana\u00efs","family":"Varlet","sequence":"first","affiliation":[{"name":"Aix Marseille Univ, INSERM, MMG, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9948-687X","authenticated-orcid":false,"given":"Camille","family":"Desgrouas","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, MMG, 13385 Marseille, France"},{"name":"Aix Marseille Univ, Laboratoire de Chimie Analytique, Facult\u00e9 de Pharmacie, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5888-1064","authenticated-orcid":false,"given":"C\u00e9cile","family":"Jebane","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, CNRS, CINAM, Turing Centre for Living Systems, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bonello-Palot","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, MMG, 13385 Marseille, France"},{"name":"APHM, Department of Genetics, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, MMG, 13385 Marseille, France"},{"name":"APHM, Department of Genetics, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Levy","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, MMG, 13385 Marseille, France"},{"name":"APHM, Department of Genetics, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-0964","authenticated-orcid":false,"given":"Emmanu\u00e8le","family":"Helfer","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, CNRS, CINAM, Turing Centre for Living Systems, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mie","family":"Dubois","sequence":"additional","affiliation":[{"name":"APHM, Metabolic Diseases, Endocrinology, Department of Nutrition, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2176-3280","authenticated-orcid":false,"given":"Ren\u00e9","family":"Valero","sequence":"additional","affiliation":[{"name":"APHM, Metabolic Diseases, Endocrinology, Department of Nutrition, 13385 Marseille, France"},{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Badens","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, MMG, 13385 Marseille, France"},{"name":"APHM, Department of Genetics, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Beliard","sequence":"additional","affiliation":[{"name":"APHM, Metabolic Diseases, Endocrinology, Department of Nutrition, 13385 Marseille, France"},{"name":"Aix Marseille Univ, INSERM, INRAE, C2VN, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/nrendo.2010.199","article-title":"Lipodystrophy: Pathophysiology and advances in treatment","volume":"7","author":"Fiorenza","year":"2011","journal-title":"Nat. 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