Jiang Jingjing, Wang Yuhui, Ling Yan, Kayoumu Abudurexiti, Liu George, Gao Xin
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
Institute of Cardiovascular Science, Peking University and Key laborotory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Lipids Health Dis. 2016 Jan 16;15:12. doi: 10.1186/s12944-015-0171-6.
The severe forms of hypertriglyceridemia are usually caused by genetic defects. In this study, we described a Chinese female with severe hypertriglyceridemia caused by a novel homozygous mutation in the APOC2 gene.
Lipid profiles of the pedigree were studied in detail. LPL and HL activity were also measured. The coding regions of 5 candidate genes (namely LPL, APOC2, APOA5, LMF1, and GPIHBP1) were sequenced using genomic DNA from peripheral leucocytes. The ApoE gene was also genotyped.
Serum triglyceride level was extremely high in the proband, compared with other family members. Plasma LPL activity was also significantly reduced in the proband. Serum ApoCII was very low in the proband as well as in the heterozygous mutation carriers. A novel mutation (c.86A > CC) was identified on exon 3 [corrected] of the APOC2 gene, which converted the Asp [corrected] codon at position 29 into Ala, followed by a termination codon (TGA).
This study presented the first case of ApoCII deficiency in the Chinese population, with a novel mutation c.86A > CC in the APOC2 gene identified. Serum ApoCII protein might be a useful screening test for identifying mutation carriers.
严重的高甘油三酯血症通常由基因缺陷引起。在本研究中,我们描述了一名中国女性,其严重高甘油三酯血症由载脂蛋白C2(APOC2)基因的一种新型纯合突变所致。
详细研究了该家系的血脂谱。还测定了脂蛋白脂肪酶(LPL)和肝脂酶(HL)活性。使用外周血白细胞的基因组DNA对5个候选基因(即LPL、APOC2、载脂蛋白A5(APOA5)、脂酶成熟因子1(LMF1)和糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(GPIHBP1))的编码区进行测序。同时对载脂蛋白E(ApoE)基因进行基因分型。
与其他家庭成员相比,先证者的血清甘油三酯水平极高。先证者的血浆LPL活性也显著降低。先证者以及杂合突变携带者的血清载脂蛋白CII水平都非常低。在APOC2基因第3外显子[已校正]上鉴定出一种新型突变(c.86A>CC),该突变将第29位的天冬氨酸[已校正]密码子转换为丙氨酸,随后是终止密码子(TGA)。
本研究报道了中国人群中首例载脂蛋白CII缺乏症病例,鉴定出APOC2基因的新型突变c.86A>CC。血清载脂蛋白CII蛋白可能是识别突变携带者的一种有用筛查检测方法。