{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T02:34:48Z","timestamp":1769308488335,"version":"3.49.0"},"reference-count":24,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T00:00:00Z","timestamp":1731196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Familial partial lipodystrophies (FPLDs) are very rare inherited disorders characterized by partial loss of adipose tissue from the upper and lower extremities. At least seven subtypes of FPLD have been identified and are mostly dominantly inherited. FPLD type 3 is caused by mutations in the PPAR\u03b3 gene, which encodes for the protein peroxisome proliferator-activated receptor gamma (PPAR\u03b3). We identified a Saudi female with PFLD3 presented with partial lipoatrophy, uncontrolled diabetes, severe hypertriglyceridemia, and recurrent pancreatitis. The clinical and biochemical findings in this proband were described before and after treatment with Pioglitazone in addition to the conventional treatment. DNA extraction and whole exome sequencing (WES) were performed to detect the variant. The mutant gene was subjected to Sanger analysis to confirm the results. We applied five specific computational prediction tools to assess the pathogenicity of variation, namely the MT, DANN, CADD, BayesDel, and fitCons tools. We assessed protein modeling and stability with the AlphaFold-generated structures for both wild-type and mutant proteins. Finally, we conducted molecular docking using the AutoDock Vina virtual docking. Upon whole exome sequencing, a c.1024C&gt;T p.(Gln342Ter) missense mutation was detected in the PPAR\u03b3 gene associated with FPLD3. This variant is a novel mutation that has not been described in all genome databases. Sanger analysis confirmed the heterogenicity and pathogenicity of this variant. All five computational prediction tools indicate that this variant is considered highly pathogenic. Our patient showed a dramatic response to Pioglitazone, a synthetic PPAR\u03b3 agonist. From structural modeling, we found that the enhanced binding affinity of the mutant PPAR\u03b3 protein to Pioglitazone likely improves the activation of PPAR\u03b3, enhancing its transcriptional activity and resulting in better clinical outcomes. These findings extend the spectrum of PPAR\u03b3 mutations responsible for FPLD3 and highlight the potential for personalized treatment strategies based on genetic mutations.<\/jats:p>","DOI":"10.3390\/ijms252212060","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"12060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genomic and Bioinformatics Analysis of Familial Partial Lipodystrophy Type 3 Identified in a Patient with Novel PPAR\u03b3 Mutation and Robust Response to Pioglitazone"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-4439","authenticated-orcid":false,"given":"Abdulrahman","family":"Hummadi","sequence":"first","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0733-5463","authenticated-orcid":false,"given":"Saeed","family":"Yafei","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"},{"name":"Endocrinology Department, Faculty of Medicine and Health Sciences, Taiz University, Taiz 11712, Yemen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhayf Alrahman","family":"Mutawwam","sequence":"additional","affiliation":[{"name":"Molecular Genetics Department, Jazan Health Affairs, Ministry of Health, Jazan 82617, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raed","family":"Abutaleb","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-1441","authenticated-orcid":false,"given":"Yahia","family":"Solan","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah","family":"Khawaji","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3955-2975","authenticated-orcid":false,"given":"Ali Jaber","family":"Alhagawy","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Turki","family":"Algohani","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamdouh","family":"Khardali","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Hakami","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulrraheem","family":"Daghriri","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wegdan","family":"Hezam","sequence":"additional","affiliation":[{"name":"Altewal Hospital, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nourah","family":"Kariri","sequence":"additional","affiliation":[{"name":"Adult Endocrinology and Diabetes, Jazan Endocrinology & Diabetes Center, Ministry of Health, Jazan 82723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1056\/NEJMra025261","article-title":"Acquired and inherited lipodystrophies","volume":"350","author":"Garg","year":"2004","journal-title":"N. 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