Clinical presentations,metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy |
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| Affiliation: | 1. Division of Endocrinology, Dokuz Eylul University, Izmir, Turkey;2. Department of Medical Genetics, Ege University, Izmir, Turkey;3. Division of Pediatric Endocrinology, Dr. Sami Ulus Obstetrics and Gynecology, Children''s Health and Disease Training and Research Hospital, Ankara, Turkey;4. Division of Endocrinology, Mersin University, Mersin, Turkey;5. Division of Endocrinology, Ege University, Izmir, Turkey;6. Division of Endocrinology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey;7. Mus Public Hospital, Mus, Turkey;8. Division of Endocrinology, Capa Faculty of Medicine, Istanbul University, Istanbul, Turkey;9. Pamukkale University, Denizli, Turkey;10. Diyarbakir Training Hospital, Diyarbakir, Turkey;11. Division of Pediatric Genetics, Ege University, Izmir, Turkey;12. Division of Pediatric Endocrinology, Ege University, Izmir, Turkey;13. Department of Radiology, Dokuz Eylul University, Izmir, Turkey;14. Division of Pediatric Neurology, Dr.Behcet Uz Children''s Hospital, Izmir, Turkey;15. Department of Biochemistry, Ataturk Training Hospital, Izmir, Turkey;p. Division of Endocrinology and Metabolism, Brehm Center for Diabetes Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA;1. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC 3168, Australia;2. Diabetes and Vascular Medicine Unit, Monash Health, Locked Bag 29, Clayton, VIC 3168, Australia;1. Department of Clinical Endocrinology and Nutrition, Institute of Biomedical Research of Málaga (IBIMA), Hospital of Málaga (Virgen de la Victoria), University of Málaga (UMA), Málaga, Spain;2. CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Spain;3. Research Laboratory, Science School, University of Málaga (UMA), Campus Teatinos s/n, 29010 Málaga, Spain;4. Lipids and Atherosclerosis Unit, Maimonides Institute of Biomedical Research of Córdoba, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain;1. Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME, USA;2. Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME, USA;3. Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA;4. Diabetes Unit, Massachusetts General Hospital, Boston, MA;5. Department of Medicine, Beth Israel Deaconess Hospital, Boston, MA, USA;6. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA;1. Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828;2. Diabetes Centre, Khoo Teck Puat Hospital, Singapore 768828;3. Division of Endocrinology, Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828;4. Division of Nephrology, Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828;5. Yishun Polyclinic, National Healthcare Group, Singapore 768796;1. Department of Public Health and Clinical Medicine, Umeå University;2. Institute of Neuroscience and Physiology, University of Gothenburg;3. Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden;4. Department of Endocrinology, Skåne University Hospital, Malmö, Sweden;5. UKK Institute for Health Promotion Research, Tampere, Finland,;6. National Institute for Health and Welfare, Helsinki, Finland;1. Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands;2. Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands |
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| Abstract: | ObjectiveFamilial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat.MethodsThis multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison.ResultsPathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed.ConclusionWe have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity. |
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