Baris Akinci1, Huseyin Onay2, Tevfik Demir3, Şenay Savas-Erdeve4, Ramazan Gen5, Ilgin Yildirim Simsir6, Fatma Ela Keskin7, Mehmet Sercan Erturk8, Ayse Kubat Uzum9, Guzin Fidan Yaylali10, Nilufer Kutbay Ozdemir11, Tahir Atik12, Samim Ozen13, Banu Sarer Yurekli6, Tugce Apaydin7, Canan Altay14, Gulcin Akinci15, Leyla Demir16, Abdurrahman Comlekci3, Mustafa Secil14, Elif Arioglu Oral17. 1. Division of Endocrinology, Dokuz Eylul University, Izmir, Turkey. Electronic address: barisakincimd@gmail.com. 2. Department of Medical Genetics, Ege University, Izmir, Turkey. 3. Division of Endocrinology, Dokuz Eylul University, Izmir, Turkey. 4. Division of Pediatric Endocrinology, Dr. Sami Ulus Obstetrics and Gynecology, Children's Health and Disease Training and Research Hospital, Ankara, Turkey. 5. Division of Endocrinology, Mersin University, Mersin, Turkey. 6. Division of Endocrinology, Ege University, Izmir, Turkey. 7. Division of Endocrinology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. 8. Mus Public Hospital, Mus, Turkey. 9. Division of Endocrinology, Capa Faculty of Medicine, Istanbul University, Istanbul, Turkey. 10. Pamukkale University, Denizli, Turkey. 11. Diyarbakir Training Hospital, Diyarbakir, Turkey. 12. Division of Pediatric Genetics, Ege University, Izmir, Turkey. 13. Division of Pediatric Endocrinology, Ege University, Izmir, Turkey. 14. Department of Radiology, Dokuz Eylul University, Izmir, Turkey. 15. Division of Pediatric Neurology, Dr.Behcet Uz Children's Hospital, Izmir, Turkey. 16. Department of Biochemistry, Ataturk Training Hospital, Izmir, Turkey. 17. Division of Endocrinology and Metabolism, Brehm Center for Diabetes Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Abstract
OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic 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. CONCLUSION: We 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.
OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic 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 LMNAp.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. CONCLUSION: We 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.
Authors: Natalia Xavier S de Andrade; Suleyman Cem Adiyaman; Berna Demir Yuksel; Carla T Ferrari; Abdelwahab Jalal Eldin; Basak Ozgen Saydam; Canan Altay; Pratima Sharma; Nicole Bhave; Ann Little; Paul McKeever; Huseyin Onay; Sermin Ozkal; Mustafa Secil; Mustafa Nuri Yenerel; Baris Akinci; Elif A Oral Journal: AACE Clin Case Rep Date: 2020-03-04
Authors: Elif A Oral; Phillip Gorden; Elaine Cochran; David Araújo-Vilar; David B Savage; Alison Long; Gregory Fine; Taylor Salinardi; Rebecca J Brown Journal: Endocrine Date: 2019-02-25 Impact factor: 3.633