{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:37:54Z","timestamp":1792244274850,"version":"4.4.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01-DK105448"],"award-info":[{"award-number":["R01-DK105448"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1U54HG006493"],"award-info":[{"award-number":["1U54HG006493"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019039","name":"University of Washington Center for Mendelian Genomics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019039","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014895","name":"Southwest Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100030692","name":"Intramural Research Program of the","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021453","name":"US government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"US Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome is a rare, autosomal dominant disorder due to pathogenic heterozygous variants in POLD1. Clinical features of MDPL vary between patients; however, there is no previously reported genotype-phenotype association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This work reports 14 new patients with lipodystrophy due to POLD1 variants and compares phenotypic differences between those with p.Ser605del and missense variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genetic sequencing was performed on DNA of 14 patients for POLD1 variants, including exome (n = 10), genome (n = 1), and candidate gene (n = 3) sequencing. Comparisons of demographic, clinical features, and metabolic complications between carriers of POLD1 p.Ser605del and missense variants in our cases and those reported in the literature were made using the Fisher exact test for categorical variables and the t test for continuous variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 9 different POLD1 variants were identified in our patients, including 3 novel variants: p.Asp25Glufs*16, p.Arg507His, and p.Trp781Cys. Compared to individuals with missense variants (n = 15), those with the p.Ser605del (n = 26) POLD1 variant had significantly increased prevalence of mandibular hypoplasia (57% vs 100%, respectively; P = .015), small mouth (36% vs 100%, respectively; P = .015), crowded teeth (44% vs 91%, respectively; P = .046), and hypogonadism in male patients (0% vs 92%, respectively; P = .046). There were no differences in the prevalence of metabolic complications, such as diabetes, hypertriglyceridemia, and hepatic steatosis, in the two groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Individuals with the heterozygous POLD1 p.Ser605del variant had typical MDPL with more severe phenotype compared to those with missense variants with atypical MDPL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag079","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:41:05Z","timestamp":1771936865000},"page":"2378-2388","source":"Crossref","is-referenced-by-count":1,"title":["Genotype-phenotype heterogeneity among patients with lipodystrophy harboring rare\n                    <i>POLD1<\/i>\n                    variants"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-1255","authenticated-orcid":false,"given":"Fieke W","family":"Hoff","sequence":"first","affiliation":[{"name":"Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xing","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, UT Southwestern Medical Center , Dallas, TX 75390-8591 ,","place":["USA"]},{"name":"Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center , Dallas, TX 75390 ,","place":["USA"]},{"name":"O\u2019Donnell School of Public Health, UT Southwestern Medical Center , Dallas, TX 75390-9066 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, UT Southwestern Medical Center , Dallas, TX 75390-8591 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-2832","authenticated-orcid":false,"given":"Vinaya","family":"Simha","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-7382","authenticated-orcid":false,"given":"Rebecca J","family":"Brown","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 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