Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia
Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia
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DOI：
10.1186/1476-511x-7-3
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发表时间：
2008-01-31
影响因子：
4.5
通讯作者：
Hegele, Robert A.
中科院分区：
文献类型：
--
作者：
Cao, Henian;Alston, Lindsay;Hegele, Robert A.
背景：编码caveolin-1的Cav1基因缺失的小鼠发生脂肪细胞异常和胰岛素抵抗。我们利用DNA序列分析技术，从非典型脂肪营养不良和高脂血症患者的基因组DNA中筛选出人CAV 1的编码区，（MIM 601047）。结果：我们在一名患有非典型部分脂肪营养不良的女性患者中发现了CAV 1中的杂合移码突变，命名为1134fsdelA-X137，皮下脂肪的减少影响了她身体的上部和脸部，但保留了她的腿、臀部和内脏脂肪储存。她患有严重的5型高脂蛋白血症，并伴有复发性胰腺炎。此外，她有一些非典型特征，包括先天性白内障和神经系统检查结果。她的父亲也是这种突变的杂合子，有类似的脂肪再分布模式，高脂血症和先天性白内障，伴有轻度神经系统受累。一个无关的患者在CAV 1基因中有一个不同的杂合移码突变，命名为-88delC。他还患有部分脂肪营养不良表型，皮下脂肪减少影响手臂，腿部和臀部，但保留了他的面部，颈部和内脏脂肪储存。他还患有重度5型高脂蛋白血症，伴复发性胰腺炎;但他没有临床上明显的神经系统表现。结论：因此，非常罕见的CAV 1移码突变似乎与非典型脂肪营养不良和高脂血症。
Background: Mice with a deleted Cav1 gene encoding caveolin-1 develop adipocyte abnormalities and insulin resistance. From genomic DNA of patients with atypical lipodystrophy and hypertriglyceridemia who had no mutations in any known lipodystrophy gene, we used DNA sequence analysis to screen the coding regions of human CAV1 (MIM 601047).Results: We found a heterozygous frameshift mutation in CAV1, designated 1134fsdelA-X137, in a female patient who had atypical partial lipodystrophy, with subcutaneous fat loss affecting the upper part of her body and face, but sparing her legs, gluteal region and visceral fat stores. She had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis. In addition, she had some atypical features, including congenital cataracts and neurological findings. Her father was also heterozygous for this mutation, and had a similar pattern of fat redistribution, hypertriglyceridemia and congenital cataracts, with milder neurological involvement. An unrelated patient had a different heterozygous frameshift mutation in the CAV1 gene, designated -88delC. He also had a partial lipodystrophy phenotype, with subcutaneous fat loss affecting the arms, legs and gluteal region, but sparing his face, neck and visceral fat stores. He also had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis; however he had no clinically apparent neurological manifestations. The mutations were absent from the genomes of 1063 healthy individuals.Conclusion: Thus, very rare CAV1 frameshift mutations appear to be associated with atypical lipodystrophy and hypertriglyceridemia.