LMNA, PPARG AND PLIN1 GENE ANALYSIS IN FAMILIAL PARTIAL LIPODYSTROPHY
Familial Partial Lipodystrophy (FPLD) is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution beginning in late childhood or early adult life. Affected individuals gradually lose fat from the upper and lower extremities and the gluteal and truncal regions, resulting in a muscular appearance with prominent superficial veins. In some patients, adipose tissue accumulates on the face and neck, causing a double chin, fat neck, or cushingoid appearance. Metabolic abnormalities include insulin-resistant diabetes mellitus with acanthosis nigricans and hypertriglyceridemia; hirsutism and menstrual abnormalities occur infrequently.
FPLD is a clinically and genetically heterogeneous disorder, caused by variants in the LMNA, PPARG and PLIN1 genes (Shackleton et al 2000 Nat Genet 24: 153-158, Barroso et al 1999 Nature 402: 880-883, Gandotra et al 2011 N Engl J Med 364: 740-748). LMNA gene variants are the most common cause of FPLD, and missense variants of the arginine residue at codon 482 of LMNA account for 90% of FPLD type 2 families. Disease-causing LMNA variants not at position p.R482 are associated with severe metabolic alterations (metabolic laminopathy) but with clinically less obvious lipodystrophy (Decaudain et al 2007 J Clin Enodcrinol Metab 92: 4835-4844; Dutour et al 2011 Hum Mol Genet 20: 3779-3786).
The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.
Information on the National Severe Insulin Resistance Service which provides investigation and management services for this and associated conditions at Addenbrooke’s Hospital (Cambridge) is available from the following link:
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