title: Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC.
abstract: 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 premature truncation mutation in the lipid droplet protein cell death-inducing Dffa-like effector C (CIDEC) (E186X). The truncation disrupts the highly conserved CIDE-C domain and the mutant protein is mistargeted and fails to increase the lipid droplet size in transfected cells. In mice, Cidec deficiency also reduces fat mass and induces the formation of white adipocytes with multilocular lipid droplets, but in contrast to our patient, Cidec null mice are protected against diet-induced obesity and insulin resistance. In addition to describing a novel autosomal recessive form of familial partial lipodystrophy, these observations also suggest that CIDEC is required for unilocular lipid droplet formation and optimal energy storage in human fat.
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
authors.forename: Oscar
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authors.lastname: Rubio-Cabezas
authors.forename: Vishwajeet
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authors.lastname: Puri
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authors.lastname: Semple
authors.forename: Satya
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authors.lastname: Dash
authors.forename: Caroline S S
authors.initials: CS
authors.lastname: Hyden
authors.forename: William
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authors.lastname: Bottomley
authors.forename: Corinne
authors.initials: C
authors.lastname: Vigouroux
authors.forename: Jocelyne
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authors.lastname: Magré
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authors.lastname: Raymond-Barker
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authors.lastname: Murgatroyd
authors.forename: Anil
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authors.lastname: Chawla
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authors.lastname: Skepper
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authors.initials: VK
authors.lastname: Chatterjee
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authors.lastname: Suliman
authors.forename: Ann-Marie
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authors.lastname: Patch
authors.forename: Anil K
authors.initials: AK
authors.lastname: Agarwal
authors.forename: Abhimanyu
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authors.lastname: Garg
authors.forename: Inês
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authors.lastname: Barroso
authors.forename: Saverio
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authors.lastname: Cinti
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czech
authors.forename: Jesús
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authors.lastname: Argente
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: David B
authors.initials: DB
authors.lastname: Savage
mesh_terms: D016475:3T3 Cells; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D018389:Codon, Nonsense; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D021381:Protein Transport; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C472088:CIDEC protein, human; D018389:Codon, Nonsense; D011506:Proteins