{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:04:06Z","timestamp":1790024646979,"version":"4.0.1"},"reference-count":23,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T00:00:00Z","timestamp":1617408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431B 2020\/37"],"award-info":[{"award-number":["ED431B 2020\/37"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI081449"],"award-info":[{"award-number":["PI081449"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Asociaci\u00f3n Espa\u00f1ola de Familiares y Afectados de Lipodistrofias (AELIP)","award":["Research Fellowship"],"award-info":[{"award-number":["Research Fellowship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Type 2 familial partial lipodystrophy, or Dunnigan disease, is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution. This rare condition results from variants principally affecting exons 8 and 11 of the LMNA gene. In this study, five FPLD2-diagnosed patients carrying the c.1583C&gt;T, p.(Thr528Met) variant in exon 9 of the LMNA gene and with obvious clinical heterogeneity were evaluated. Specific polymorphisms in LMNA and in PPARG were also detected. Exhaustive clinical course, physical examination, biochemical features and family history were recorded, along with the assessment of anthropometric features and body composition by dual-energy X-ray absorptiometry. Preadipocytes obtained from a T528M patient were treated with the classic adipose differentiation medium with pioglitazone. Various adipogenes were evaluated by real-time PCR, and immunofluorescence was used to study intracellular localization of emerin, lamin A and its precursors. As demonstrated with Oil red O staining, the preadipocytes of the T528M patient failed to differentiate, the expression of various adipogenic genes was reduced in the lipodystrophic patient and immunofluorescence studies showed an accumulation of farnesylated prelamin A in T528M cells. We conclude that the T528M variant in LMNA could lead to FPLD2, as the adipogenic machinery is compromised.<\/jats:p>","DOI":"10.3390\/jcm10071497","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T22:03:36Z","timestamp":1617487416000},"page":"1497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2852-7851","authenticated-orcid":false,"given":"David","family":"Ara\u00fajo-Vilar","sequence":"first","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1268-7538","authenticated-orcid":false,"given":"Ant\u00eda","family":"Fern\u00e1ndez-Pombo","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Victoria","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Mosquera-Orgueira","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-626X","authenticated-orcid":false,"given":"Silvia","family":"Cobelo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Castro-Pais","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBERobn), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-262X","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Hermida-Ameijeiras","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Division of Internal Medicine, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Loidi","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Galega de Medicina Xen\u00f3mica, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3887-0573","authenticated-orcid":false,"given":"Sof\u00eda","family":"S\u00e1nchez-Iglesias","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00125-004-1360-4","article-title":"Familial partial lipodystrophy associated with compound heterozygosity for novel mutations in the LMNA gene","volume":"47","author":"Savage","year":"2004","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1093\/hmg\/ddl172","article-title":"Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation","volume":"15","author":"Verstraeten","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med. Off. J. Am. Coll. Med Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: Improving access to variant interpretations and supporting evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: The NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1093\/ajcn\/51.6.1106","article-title":"Dual-energy x-ray absorptiometry for total-body and regional bone-mineral and soft-tissue composition","volume":"51","author":"Mazess","year":"1990","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1055\/s-2003-38388","article-title":"Phenotypic gender differences in subjects with familial partial lipodystrophy (Dunnigan variety) due to a nuclear lamin A\/C R482W mutation","volume":"35","author":"Loidi","year":"2003","journal-title":"Horm. Metab. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9670","DOI":"10.1074\/jbc.M007454200","article-title":"Cholesterol depletion disrupts caveolae and insulin receptor signaling for metabolic control via insulin receptor substrate-1, but not for mitogen-activated protein kinase control","volume":"276","author":"Parpal","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sanchez-Iglesias, S., Unruh-Pinheiro, A., Guillin-Amarelle, C., Gonzalez-Mendez, B., Ruiz-Riquelme, A., Rodriguez-Canete, B.L., Rodriguez-Garcia, S., Guillen-Navarro, E., Domingo-Jimenez, R., and Araujo-Vilar, D. (2016). Skipped BSCL2 Transcript in Celia\u2019s Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158874"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4081\/ejh.2009.e6","article-title":"Different prelamin A forms accumulate in human fibroblasts: A study in experimental models and progeria","volume":"53","author":"Dominici","year":"2009","journal-title":"Eur. J. Histochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5065","DOI":"10.3892\/mmr.2015.4065","article-title":"Cardiac effects of the c.1583 C-->G LMNA mutation in two families with Emery-Dreifuss muscular dystrophy","volume":"12","author":"Zhang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1086\/341908","article-title":"Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A\/C","volume":"71","author":"Novelli","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5259","DOI":"10.1210\/jc.2004-2560","article-title":"A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia","volume":"90","author":"Garg","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1002\/ajmg.a.31983","article-title":"Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes","volume":"143A","author":"Kosho","year":"2007","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1006\/bbrc.2000.2096","article-title":"Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis","volume":"268","author":"Masugi","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/j.1365-2265.2011.04208.x","article-title":"Histological and molecular features of lipomatous and nonlipomatous adipose tissue in familial partial lipodystrophy caused by LMNA mutations","volume":"76","author":"Victoria","year":"2012","journal-title":"Clin. Endocrinol."},{"key":"ref_20","first-page":"40","article-title":"Site-dependent differences in both prelamin A and adipogenic genes in subcutaneous adipose tissue of patients with type 2 familial partial lipodystrophy","volume":"46","author":"Lattanzi","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1083\/jcb.201701043","article-title":"A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus","volume":"216","author":"Oldenburg","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1093\/hmg\/ddi158","article-title":"Altered pre-lamin A processing is a common mechanism leading to lipodystrophy","volume":"14","author":"Capanni","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1038\/sj.cdd.4402197","article-title":"Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence","volume":"14","author":"Caron","year":"2007","journal-title":"Cell Death Differ."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/7\/1497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:15Z","timestamp":1760361975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/7\/1497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,3]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["jcm10071497"],"URL":"https:\/\/doi.org\/10.3390\/jcm10071497","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,3]]}}}