{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:06:31Z","timestamp":1791389191310,"version":"4.3.3"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2017L8Z2EM"],"award-info":[{"award-number":["2017L8Z2EM"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. We herein examine the case of a patient carrying a heterozygous LMNA c.1634G&gt;A (p.R545H) variant with a mild, transient myopathy, who was referred to our center for the suspicion of lipodystrophy. At physical examination, an abnormal distribution of subcutaneous fat was noticed, with fat accumulation in the anterior regions of the neck, resembling the fat distribution pattern of familial partial lipodystrophy type 2 (FPLD2). The R545H missense variant has been found at very low allelic frequency in public databases, and in silico analysis showed that this amino acid substitution is predicted to have a damaging role. Other patients carrying the heterozygous LMNA p.R545H allele have shown a marked clinical heterogeneity in terms of phenotypic body fat distribution and severity of organ system involvement. These findings indicate that the LMNA p.R545H heterozygous variant exhibits incomplete penetrance and highly variable expressivity. We hypothesized that additional genetic factors, epigenetic mechanisms, or environmental triggers might explain the variable expressivity of phenotypes among various patients.<\/jats:p>","DOI":"10.3390\/jcm10051142","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T06:22:32Z","timestamp":1615270952000},"page":"1142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Partial Lipodystrophy and LMNA p.R545H Variant"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8705-6554","authenticated-orcid":false,"given":"Silvia","family":"Magno","sequence":"first","affiliation":[{"name":"Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0701-642X","authenticated-orcid":false,"given":"Giovanni","family":"Ceccarini","sequence":"additional","affiliation":[{"name":"Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-340X","authenticated-orcid":false,"given":"Andrea","family":"Barison","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"},{"name":"Institute of Life Sciences, Scuola Superiore Sant\u2019Anna, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Fabiani","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Giacomina","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Unit, Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Gilio","sequence":"additional","affiliation":[{"name":"Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Pelosini","sequence":"additional","affiliation":[{"name":"Chemistry and Endocrinology Laboratory, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rubegni","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Emdin","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"},{"name":"Institute of Life Sciences, Scuola Superiore Sant\u2019Anna, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Luca","family":"Gatti","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Unit, Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-9062","authenticated-orcid":false,"given":"Filippo Maria","family":"Santorelli","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Sessa","sequence":"additional","affiliation":[{"name":"Chemistry and Endocrinology Laboratory, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1706-0822","authenticated-orcid":false,"given":"Ferruccio","family":"Santini","sequence":"additional","affiliation":[{"name":"Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","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. 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