1. Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy
- Author
-
Ilgin Yildirim Simsir, Tevfik Demir, Leyla Demir, Hüseyin Onay, Fatma Ela Keskin, Guzin Fidan Yaylali, Mehmet Sercan Erturk, Ayse Kubat Uzum, Gulcin Akinci, Samim Özen, Ramazan Gen, Canan Altay, Şenay Savas-Erdeve, Mustafa Secil, Abdurrahman Comlekci, Tugce Apaydin, Nilüfer Özdemir, Banu Sarer Yurekli, Elif A. Oral, Tahir Atik, and Baris Akinci
- Subjects
0301 basic medicine ,Male ,Lipodystrophy ,subcutaneous fat ,Turkey ,Endocrinology, Diabetes and Metabolism ,LMNA ,Exon ,0302 clinical medicine ,Endocrinology ,high density lipoprotein cholesterol ,cardiovascular disease ,fat ,insulin resistance ,familial partial lipodystrophy ,genetic variability ,pulmonary hypertension ,middle aged ,Missense mutation ,Body Fat Distribution ,tricuspid valve regurgitation ,genetics ,exon ,nuclear magnetic resonance imaging ,Lamin Type B ,adult ,Diabetes ,Genetic disorder ,peroxisome proliferator activated receptor gamma ,clinical trial ,genetic screening ,Lamin Type A ,Magnetic Resonance Imaging ,Lipodystrophy, Familial Partial ,female ,priority journal ,PPARG ,point mutation ,prospective study ,medicine.medical_specialty ,acute pancreatitis ,hypertriglyceridemia ,heart infarction ,Mutation, Missense ,rare disease ,030209 endocrinology & metabolism ,complication ,Biology ,leptin ,Article ,03 medical and health sciences ,peroxisome proliferator activated receptor gamma coactivator 1alpha ,Internal medicine ,ovary polycystic disease ,medicine ,LMNA protein, human ,Humans ,controlled study ,human ,lamin B ,gene ,lamin B1 ,lamin A ,Adult ,Case-Control Studies ,Female ,Insulin Resistance ,Lamin Type A/*genetics ,Lamin Type B/genetics ,Lipodystrophy, Familial Partial/complications/genetics/*pathology ,Middle Aged ,PPAR gamma/*genetics ,controlled clinical trial ,Genetic heterogeneity ,Point mutation ,missense mutation ,case control study ,medicine.disease ,Familial partial lipodystrophy ,major clinical study ,clinical feature ,PPAR gamma ,030104 developmental biology ,multicenter study ,observational study ,pathology ,codon ,proteinuria ,metabolism - 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.
- Published
- 2017