Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation
Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation
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DOI：
10.1016/j.cca.2011.11.020
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发表时间：
2012-03-22
影响因子：
5
通讯作者：
Blanco-Vaca, Francisco
中科院分区：
文献类型：
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作者：
Martin-Campos, Jesus M.;Roig, Rosa;Blanco-Vaca, Francisco
背景：家族性低β脂蛋白血症(FHBL)以血浆载脂蛋白B(ApoB)和低密度脂蛋白(LDLc)相关的胆固醇水平极低为特征，被认为是一种异质性的常染色体共显性疾病。与FHBL相关的主要遗传性疾病包括APOB基因突变，而其他较不常见的形式与NPC1L1、PCSK9、3p21.1-22和最近的ANGPTL3基因突变有关。方法：我们扫描了4个符合FHBL标准但APOB突变阴性的无关西班牙家庭的Angptl3突变。结果：两个先证者检测到相同的移码突变，其第121位密码子缺失5个碱基，产生一个122个残基的截短蛋白。结论：我们证实存在一种新的FHBL表型，即家族性混合性低脂血症，该表型包括低低密度脂蛋白、低载脂蛋白B、低甘油三酯，其生化表型为低低密度脂蛋白、低载脂蛋白B、低甘油三酯，与载脂蛋白B突变不同，由于Angptl3功能丧失突变，低高密度脂蛋白胆固醇降低。(C)2011爱思唯尔B.V.保留所有权利。
Background: Familial hypobetalipoproteinemia (FHBL), characterized by extremely low levels of plasma apolipoprotein (apo) B and cholesterol associated with low-density lipoproteins (LDLc), is considered to be an autosomal co-dominant disorder of heterogeneous origin. The main genetic disorder associated with FHBL consists of mutations in the APOB gene, while other less frequent forms are associated with mutations in NPC1L1, PCSK9, a still unidentified gene in 3p21.1-22 and, more recently, in ANGPTL3.Methods: We scanned for ANGPTL3 mutations in 4 unrelated Spanish families with FHBL criteria but negative for mutations in APOB. The entire coding region and intron-exon boundaries of the ANGPTL3 gene were amplified and sequenced.Results: Two probands were positive for the same frameshift mutation, a deletion of 5 bp in codon 121 in ANGPTL3, which produces a truncated protein of 122 residues. This mutation in homozygosis was associated in both families with combined hypolipidemia, characterized by low plasma apoB, low total, LDL and HDL cholesterol and low triglycerides.Conclusion: We confirm the existence of a new phenotype of FHBL, denominated familial combined hypolipidemia, which consist of a biochemical phenotype of low LDLc, low apoB, low TG and, unlike APOB mutations, low HDL cholesterol, due to a loss-of-function mutation in ANGPTL3. (C) 2011 Elsevier B.V. All rights reserved.