Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC

Lipodystrophic syndromes are characterized by adipose tissue deficiency. Although rare, they are of considerable interest as they, like obesity, typically lead to ectopic lipid accumulation, dyslipidaemia and insulin resistant diabetes. In this paper we describe a female patient with partial lipodystrophy (affecting limb, femorogluteal and subcutaneous abdominal fat), white adipocytes with multiloculated lipid droplets and insulin-resistant diabetes, who was found to be homozygous for a prematuretruncationmutationinthelipiddropletproteincell death-inducingDffalike effector C (CIDEC) (E186X). Thetruncation disrupts thehighly conserved CIDE-C domainand the mutantproteinis mistargeted andfailsto increasethelipid droplet size in transfected cells. In mice, Cidec deficiency also reduces fat mass and induces