The Dunnigan syndrome [FPLD2 (familial partial lipodystrophy of the Dunnigan type)] is due to mutations in LMNA encoding the lamin A/C, belonging to the complex group of laminopathies that could comprise muscular and cardiac dystrophies, neuropathies and syndromes of premature aging.
Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-gamma.
The expression of PPARG2, RB1, CCND3 and LPL in thigh but not in abdomen scAT was significantly reduced (67%, 25%, 38% and 66% respectively) in patients with FPLD2.
The expression of PPARG2, RB1, CCND3 and LPL in thigh but not in abdomen scAT was significantly reduced (67%, 25%, 38% and 66% respectively) in patients with FPLD2.
The expression of PPARG2, RB1, CCND3 and LPL in thigh but not in abdomen scAT was significantly reduced (67%, 25%, 38% and 66% respectively) in patients with FPLD2.
Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant lamin A/C-related disease associated with exercise intolerance, muscular pain, and insulin resistance.
A homozygous mutation of prelamin-A preventing its farnesylation and maturation leads to a severe lipodystrophic phenotype: new insights into the pathogenicity of nonfarnesylated prelamin-A.
A few specific mutations in the lamin A/C gene cause a disease with remarkably different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan-type), which mainly affects adipose tissue.
The high prevalence of early and severe cardiovascular outcomes in these patients suggests that, in addition to metabolic risk factors, FPLD2-associated LMNA mutations could have a direct role on the vascular wall cells.
We propose a model where the FPLD2lamin A p.R482W mutation elicits, through up-regulation of FXR1P, a remodeling of an adipogenic differentiation program into a myogenic program.
In contrast, both overexpression of LMNAR482W in primary human preadipocytes and endogenous expression of A-type lamins R482W in FPLD2 patient fibroblasts, reduce A-type lamins-SREBP1 in situ interactions and upregulate a large number of SREBP1 target genes.