A novel heterozygous mutation in peroxisome proliferator-activated receptor-γ gene in a patient with familial partial lipodystrophy
A novel heterozygous mutation in peroxisome proliferator-activated receptor-γ gene in a patient with familial partial lipodystrophy
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DOI：
10.1210/jc.87.1.408
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发表时间：
2002-01-01
影响因子：
5.8
通讯作者：
Garg, A
中科院分区：
文献类型：
--
作者：
Agarwal, AK;Garg, A
家族性部分脂肪营养不良是一组异质性遗传性疾病，其特征是四肢皮下脂肪明显丢失。受影响的个体表现出胰岛素抵抗、糖尿病和血脂异常的优势增加。近年来，在邓尼根型FPL患者中发现核纤层蛋白A/C基因突变。然而，其他表型的遗传基础仍然未知。我们研究了过氧化物酶体增殖物激活受体-γ（PPARgamma）基因作为候选基因在7例FPL患者谁没有出现邓尼根品种。对PPARG编码区的分析显示，在患者FX 200.21中，外显子6的核苷酸1273处发生C至T杂合突变，该突变将高度保守的残基425位精氨酸改变为半胱氨酸（R425 C）。患者为64岁非西班牙裔白色女性，32岁时出现糖尿病和高脂血症，50岁时出现四肢和面部脂肪营养不良。她也有多毛症。人体测量和全身磁共振成像显示，特别是四肢的皮下脂肪明显减少，但皮下躯干脂肪略有增加。四个未受影响的家庭成员中没有一个携带突变。我们的结论是杂合子，R425 C，PPARG突变可能是家族性部分脂肪营养不良表型之一的分子基础。
Familial partial lipodystrophies (FPL) are heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. Recently, lamin A/C gene mutations were found in patients with FPL, Dunnigan variety. However, the genetic basis of other phenotypes remains unknown. We studied peroxisome proliferator-activated receptor-gamma (PPARgamma) gene as a candidate gene in seven FPL patients who did not appear to have Dunnigan variety. Analysis of the coding region of PPARG revealed C to T heterozygous mutation at nucleotide 1273 in exon 6 which changes a highly conserved residue, arginine at position 425 to cysteine (R425C) in the patient FX200.21. The patient is a 64-year-old nonHispanic white woman who developed diabetes mellitus and hypertriglyceridemia at age 32 years and lipodystrophy of the extremities and face at age 50 years. She also had hirsutism. Anthropometry and whole body magnetic resonance imaging revealed marked loss of sc fat particularly from the extremities but sc truncal fat was slightly increased. None of the four unaffected family members harbored the mutation. We conclude that heterozygous, R425C, mutation in PPARG could be the molecular basis for one of the familial partial lipodystrophy phenotype.