Identification of a novel mutation for phytosterolemia. Genetic analyses of 2 cases.
Identification of a novel mutation for phytosterolemia. Genetic analyses of 2 cases.
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DOI：
10.1016/j.cca.2008.10.026
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
M. Togo;Y. Hashimoto;N. Iso-o;M. Kurano;M. Hara;T. Kadowaki;K. Koike;K. Tsukamoto
中科院分区：
文献类型：
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作者：
M. Togo;Y. Hashimoto;N. Iso-o;M. Kurano;M. Hara;T. Kadowaki;K. Koike;K. Tsukamoto
背景植物类固醇血症是一种遗传性疾病，可导致高胆固醇血症和动脉粥样硬化，以及植物类固醇在血浆和组织中的积聚。ABCG5和ABCG8基因的突变分别编码类固醇1和2，与植物类固醇血症有关。方法我们对2例日本植物类固醇血症患者进行了基因分析。第一例患者是一种新突变的纯合子，该突变是在外显子7插入19个碱基的串联重复序列，导致在第288密码子提前终止。第二例为复合杂合子，其中一种突变与第一例相同，另一种突变是外显子10的C到T替换，导致446密码子(R446X)提前终止。在ABCG5和ABCG8基因中未发现其他突变。结论这一结果与之前发现的大多数亚洲植物类固醇血症患者存在ABCG5基因突变的观察结果一致，而且新突变的位置与以往报道的完全不同，因此有必要对植物类固醇血症进行广泛的分析。
BACKGROUNDPhytosterolemia is one of the genetic disorders causing hypercholesterolemia and atherosclerosis together with the accumulation of plant sterol in plasma and tissues. The mutations in ABCG5 and ABCG8 genes, encoding sterolin-1 and -2, respectively, are responsible for phytosterolemia.METHODSWe performed genetic analyses on 2 Japanese phytosterolemia patients.RESULTSWe identified 2 mutations in the ABCG5 gene in these patients. The first patient was homozygous for a novel mutation, which was a 19-base pair tandem repeat insertion in exon 7, leading to a premature termination at codon 288. The second patient was a compound heterozygote; one of the mutations was the same as that found in the first patient, while the other mutation was a C to T substitution in exon 10, resulting in a premature termination at codon 446 (R446X). No other mutation was found in the ABCG5 and ABCG8 genes.CONCLUSIONSThis result was concordant with previous observations that found most Asian phytosterolemia patients possessed mutations in the ABCG5 gene, and the site of the novel mutation was completely different from these previous reports, necessitating the extensive analyses for phytosterolemia.