{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:24:19Z","timestamp":1790688259354,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T00:00:00Z","timestamp":1651276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Mother\u2019s Memorial Hospital Research Institute","award":["2016\/X\/9-SZB"],"award-info":[{"award-number":["2016\/X\/9-SZB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by the selective loss of adipose tissue. Its estimated prevalence is as low as 1 in 1 million. The deficiency of metabolically active adipose tissue is closely linked with a wide range of metabolic complications, such as insulin resistance, lipoatrophic diabetes, dyslipidemia with severe hypertriglyceridemia, hypertension or hepatic steatosis. Moreover, female patients often develop hyperandrogenism, hirsutism, polycystic ovaries and infertility. The two most common types are FPLD type 2 and 3. Variants within LMNA and PPARG genes account for more than 50% of all reported FPLD cases. Because of its high heterogeneity and rarity, lipodystrophy can be easily unrecognized or misdiagnosed. To determine the genetic background of FPLD in a symptomatic woman and her close family, an NGS custom panel was used to sequence LMNA and PPARG genes. The affected patient presented fat deposits in the face, neck and trunk, with fat loss combined with muscular hypertrophy in the lower extremities and hirsutism, all features first manifesting at puberty. Her clinical presentation included metabolic disturbances, including hypercholesterolemia with severe hypertriglyceridemia, diabetes mellitus and hepatic steatosis. This together with her typical fat distribution and physical features raised a suspicion of FPLD. NGS analysis revealed the presence of missense heterozygous variant c.443G&gt;A in exon 4 of PPARG gene, causing glycine to glutamic acid substitution at amino acid position 148, p.(Gly148Glu). The variant was also found in the patient\u2019s mother and son. The variant was not previously reported in any public database. Based on computational analysis, crucial variant localization within DNA-binding domain of PPAR\u03b3, available literature data and the variant cosegregation in the patient\u2019s family, novel c.443G&gt;A variant was suspected to be causative. Functional testing is needed to confirm the pathogenicity of the novel variant. Inherited lipodystrophy syndromes represent a heterogenous group of metabolic disorders, whose background often remains unclear. A better understating of the genetic basis would allow earlier diagnosis and targeted treatment implementation.<\/jats:p>","DOI":"10.3390\/diagnostics12051122","type":"journal-article","created":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T05:44:07Z","timestamp":1651297447000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Familial Partial Lipodystrophy\u2014Literature Review and Report of a Novel Variant in PPARG Expanding the Spectrum of Disease-Causing Alterations in FPLD3"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2120-9842","authenticated-orcid":false,"given":"Lena","family":"Rutkowska","sequence":"first","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital-Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Salachna","sequence":"additional","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital-Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Lewandowski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 90-419 Lodz, Poland"},{"name":"Department of Endocrinology and Metabolic Diseases, Polish Mother\u2019s Memorial Hospital-Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8748-3337","authenticated-orcid":false,"given":"Andrzej","family":"Lewi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 90-419 Lodz, Poland"},{"name":"Department of Endocrinology and Metabolic Diseases, Polish Mother\u2019s Memorial Hospital-Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Gach","sequence":"additional","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital-Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.2147\/DMSO.S206053","article-title":"Familial Partial Lipodystrophy (FPLD): Recent Insights","volume":"13","author":"Bagias","year":"2020","journal-title":"Diabetes Metab. Syndr. Obesity Targets Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4009","DOI":"10.1172\/JCI129190","article-title":"What lipodystrophies teach us about the metabolic syndrome","volume":"129","author":"Mann","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_3","first-page":"249","article-title":"Clinical and Molecular Prevalence of Lipodystrophy in an Unascertained Large Clinical Care Cohort","volume":"69","author":"Ge","year":"2019","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.ecl.2017.01.012","article-title":"Genetics of Lipodystrophy","volume":"46","author":"Lightbourne","year":"2017","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_5","first-page":"715","article-title":"Gene-gene and gene-environment interactions in lipodystrophy: Lessons learned from natural PPAR\u03b3 mutants","volume":"1864","author":"Broekema","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Knebel, B., M\u00fcller-Wieland, D., and Kotzka, J. (2020). Lipodystrophies\u2014Disorders of the Fatty Tissue. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228778"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1242\/dmm.002907","article-title":"Mouse models of inherited lipodystrophy","volume":"2","author":"Savage","year":"2009","journal-title":"Dis. Model Mech."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1194\/jlr.M800491-JLR200","article-title":"The role of LMNA in adipose: A novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation","volume":"50","author":"Wojtanik","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/jhg.2013.107","article-title":"Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies","volume":"59","author":"Nolis","year":"2013","journal-title":"J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/hmg\/9.1.109","article-title":"Nuclear lamin A\/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy","volume":"9","author":"Cao","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Varlet, A.-A., Helfer, E., and Badens, C. (2020). Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2. Cells, 9.","DOI":"10.3390\/cells9091947"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ecl.2004.03.003","article-title":"Lipodystrophies: Rare disorders causing metabolic syndrome","volume":"33","author":"Garg","year":"2004","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/17446651.2020.1735360","article-title":"Diagnostic strategies and clinical management of lipodystrophy","volume":"15","author":"Akinci","year":"2020","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.3389\/fphys.2018.01356","article-title":"Role of Lamin A\/C Gene Mutations in the Signaling Defects Leading to Cardiomyopathies","volume":"9","author":"Gerbino","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.tem.2009.04.005","article-title":"Functional implications of genetic variation in human PPAR\u03b3","volume":"20","author":"Jeninga","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pap, A., Cuaranta-Monroy, I., Peloquin, M., and Nagy, L. (2016). Is the Mouse a Good Model of Human PPAR\u03b3-Related Metabolic Diseases?. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081236"},{"key":"ref_17","first-page":"472","article-title":"Peroxisome proliferator-activated receptors-g (PPAR-\u03b3) and their role in immunoregulation and inflammation control","volume":"3","author":"Kowalski","year":"2005","journal-title":"Post\u0119py Hig. Med. Dosw."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"816856","DOI":"10.1155\/2015\/816856","article-title":"Review of the Structural and Dynamic Mechanisms of PPAR\u03b3 Partial Agonism","volume":"2015","author":"Kroker","year":"2015","journal-title":"PPAR Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vasandani, C., Li, X., Sekizkardes, H., Brown, R., and Garg, A. (2020). SUN-LB111 Comparison of Phenotype and Metabolic Abnormalities Among Familial Partial Lipodystrophy Due to LMNA or PPARG Variants. J. Endocr. Soc., 4.","DOI":"10.1210\/jendso\/bvaa046.2312"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1210\/jc.2016-2466","article-title":"The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline","volume":"101","author":"Brown","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","unstructured":"Akinci, B., Sahinoz, M., and Oral, E. (2000). Lipodystrophy Syndromes: Presentation and Treatment. Endotext, MDText.com, Inc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2217\/clp.14.13","article-title":"Diagnosis and management of lipodystrophy: A practical update","volume":"9","author":"Stears","year":"2014","journal-title":"Clin. Lipidol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4103\/2229-5178.137765","article-title":"An approach to acanthosis nigricans","volume":"5","author":"Phiske","year":"2014","journal-title":"Indian Dermatol. Online J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/MOL.0b013e32832d4a33","article-title":"Inherited lipodystrophies and hypertriglyceridemia","volume":"20","author":"Simha","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E1676","DOI":"10.1210\/jc.2014-1878","article-title":"Lipid Regulation in Lipodystrophy versus the Obesity-Associated Metabolic Syndrome: The Dissociation of HDL-C and Triglycerides","volume":"99","author":"Joseph","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1210\/er.2010-0020","article-title":"Genetic Syndromes of Severe Insulin Resistance","volume":"32","author":"Semple","year":"2011","journal-title":"Endocr. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.metabol.2019.05.001","article-title":"Fatty liver in lipodystrophy: A review with a focus on therapeutic perspectives of adiponectin and\/or leptin replacement","volume":"96","author":"Polyzos","year":"2019","journal-title":"Metabolism"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4274\/jcrpe.galenos.2019.2019.0124","article-title":"Current Diagnosis, Treatment and Clinical Challenges in the Management of Lipodystrophy Syndromes in Children and Young People","volume":"12","author":"Ozen","year":"2020","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Arshad, M., Bhatti, A., and John, P. (2018). Identification and in silico analysis of functional SNPs of human TAGAP protein: A comprehensive study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0188143"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1475-2891-13-17","article-title":"Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications\u2014A review","volume":"13","year":"2014","journal-title":"Nutr. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"820857","DOI":"10.3389\/fphar.2022.820857","article-title":"Regulation of Lipid Metabolism by Lamin in Mutation-Related Diseases","volume":"13","author":"Peng","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.jacl.2021.07.004","article-title":"Prevalence of severe hypertriglyceridemia and pancreatitis in familial partial lipodystrophy type 2","volume":"15","author":"Lazarte","year":"2021","journal-title":"J. Clin. Lipidol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1194\/jlr.R700004-JLR200","article-title":"Thematic review series: Adipocyte Biology. Lipodystrophies: Windows on adipose biology and metabolism","volume":"48","author":"Hegele","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s40618-018-0887-z","article-title":"Diagnosis and treatment of lipodystrophy: A step-by-step approach","volume":"42","author":"Santini","year":"2019","journal-title":"J. Endocrinol. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s13105-015-0404-1","article-title":"Lipodystrophies: Adipose tissue disorders with severe metabolic implications","volume":"71","author":"Cortes","year":"2015","journal-title":"J. Physiol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cmet.2006.09.003","article-title":"Non-DNA binding, dominant-negative, human PPAR\u03b3 mutations cause lipodystrophic insulin resistance","volume":"4","author":"Agostini","year":"2006","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1007\/s00125-011-2142-4","article-title":"Characterisation of non-obese diabetic patients with marked insulin resistance identifies a novel familial partial lipodystrophy-associated PPAR\u03b3 mutation (Y151C)","volume":"54","author":"Visser","year":"2011","journal-title":"Diabetologia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1210\/jc.2005-2624","article-title":"Peroxisome Proliferator-Activated Receptor-y C190S Mutation Causes Partial Lipodystrophy","volume":"92","author":"Buettner","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:04:48Z","timestamp":1760137488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,30]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["diagnostics12051122"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12051122","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,30]]}}}