Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3) -: art. no. 3
Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3) -: art. no. 3
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DOI：
10.1186/1471-2350-7-3
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发表时间：
2006-01-14
影响因子：
--
通讯作者：
Hegele, RA
中科院分区：
文献类型：
--
作者：
Francis, GA;Li, G;Hegele, RA
背景资料：家族性部分脂肪营养不良（邓尼根）3型（FPLD 3，人类孟德尔遗传[MIM] 604367）由编码过氧化物酶体增殖物激活受体-γ的PPARG中的杂合突变引起。这两个显性负性和单倍不足的机制已被建议为this condition.Methods：我们提出了一个加拿大FPLD 3亲属与受影响的母亲谁失去了手臂和腿上的脂肪，但没有增加面部，颈部，肩胛上或腹部脂肪。她患有严重的胰岛素抵抗、糖尿病、严重的高脂血症和复发性胰腺炎，而她青春期前的女儿脂肪分布正常，但血浆甘油三酯和C肽升高，高密度脂蛋白胆固醇降低。母亲和女儿都是PPARG无义突变Y355 X的杂合子，其蛋白质产物在体外是无转录活性的，对野生型受体没有显性负活性。此外，突变蛋白似乎是显着unstable.Conclusion：与以前的研究一起，人类PPARG突变，这些研究结果表明，由于单倍不足或大量的活动损失，由于显性负干扰的正常等位基因产物的功能的PPAR-gamma缺陷可以各自有助于FPLD 3表型。
Background: 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. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition.Methods: We present a Canadian FPLD3 kindred with an affected mother who had loss of fat on arms and legs, but no increase in facial, neck, suprascapular or abdominal fat. She had profound insulin resistance, diabetes, severe hypertriglyceridemia and relapsing pancreatitis, while her prepubescent daughter had normal fat distribution but elevated plasma triglycerides and C-peptide and depressed high-density lipoprotein cholesterol.Results: The mother and daughter were each heterozygous for PPARG nonsense mutation Y355X, whose protein product in vitro was transcriptionally inactive with no dominant-negative activity against the wild-type receptor. In addition the mutant protein appeared to be markedly unstable.Conclusion: Taken together with previous studies of human PPARG mutations, these findings suggest that PPAR-gamma deficiency due either to haploinsufficiency or to substantial activity loss due to dominant negative interference of the normal allele product's function can each contribute to the FPLD3 phenotype.