Partial Lipodystrophy and LMNA p.R545H Variant
| العنوان: | Partial Lipodystrophy and LMNA p.R545H Variant |
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| المؤلفون: | Maria Rita Sessa, Gian Luca Gatti, Anna Rubegni, Giovanni Ceccarini, Ferruccio Santini, Silvia Magno, Andrea Barison, Iacopo Fabiani, Caterina Pelosini, Michele Emdin, Donatella Gilio, Alessandro Giacomina, Filippo M. Santorelli |
| المصدر: | Journal of Clinical Medicine Volume 10 Issue 5 Journal of Clinical Medicine, Vol 10, Iss 1142, p 1142 (2021) |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Familial partial lipodystrophy type 2, FPLD2, Leptin, Lipodystrophy, LMNA mutation, lipodystrophy, lcsh:Medicine, 030204 cardiovascular system & hematology, Gene mutation, leptin, Article, LMNA, 03 medical and health sciences, 0302 clinical medicine, Medicine, Missense mutation, Allele, Allele frequency, familial partial lipodystrophy type 2, 030304 developmental biology, Genetics, 0303 health sciences, integumentary system, business.industry, lcsh:R, Partial Lipodystrophy, General Medicine, medicine.disease, Penetrance, business |
| الوصف: | 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> 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2077-0383 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f4a11a6f61072342f0d3e2ada85dcd9Test http://europepmc.org/articles/PMC7963176Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9f4a11a6f61072342f0d3e2ada85dcd9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20770383 |
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