Diabetes mellitus in a new kindred with familial hypobetalipoproteinemia and an apolipoprotein B truncation (apoB-55)
Diabetes mellitus in a new kindred with familial hypobetalipoproteinemia and an apolipoprotein B truncation (apoB-55)
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DOI：
10.1016/s0021-9150(97)00222-0
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发表时间：
1998-02-01
期刊：
影响因子：
5.3
通讯作者：
Schonfeld, G
中科院分区：
文献类型：
--
作者：
Pulai, JI;Latour, MA;Schonfeld, G
家族性低脂蛋白血症是一种常染色体共显性疾病，在少数情况下是由于载脂蛋白b基因的截断产生突变。我们在一名患有2型糖尿病的40岁低脂蛋白血症患者中发现了载脂蛋白ob突变。血浆免疫印迹显示apoB-100的主要条带和apoB-52和apoB-55之间的估计大小的次要条带。先证者75岁的患有II型糖尿病的父亲和一个非糖尿病的女儿也拥有这种被截断的蛋白质。对扩增的基因组DNA片段进行直接测序，发现apoB基因26外显子nt 7692处存在C -> T过渡。这种替换在2495残基上产生了一个过早终止密码子，并消除了一个BsaI限制性内切酶位点。相同的突变之前已经被描述过；然而，基因型和祖先的亲属是不同的，表明突变可能是独立发生的。大多数apoB-55被洗脱为比LDL大小的apoB-100小的颗粒，并且主要漂浮在LDL和HDL密度范围之间。值得注意的是，尽管存在II型糖尿病，先证者及其父亲的血脂水平都很低，均未出现任何临床表现的大血管并发症。(C) 1998爱思唯尔科学爱尔兰有限公司
Familial hypobetalipoproteinemia is an autosomal co-dominant disorder, which in a minority of cases is due to a truncation producing mutation in the apoB gene. We have identified an apoB mutation in a 40-year old hypobetalipoproteinemic man with Type II diabetes mellitus. Immunoblotting of plasma revealed a major band for apoB-100 and a minor band with estimated size between apoB-52 and apoB-55. The proband's 75-year old father with Type II diabetes and a non-diabetic daughter also possessed the truncated protein. Direct sequencing of the amplified fragment of genomic DNA revealed a C --> T transition at nt 7692 in exon 26 of the apoB gene. This substitution yielded a premature stop codon at residue 2495 and abolished a BsaI restriction endonuclease site. The identical mutation has been described previously; however, the genotypes and ancestors of the kindred were different, suggesting that the mutation may have occurred independently. The majority of apoB-55 was eluted as particles smaller than LDL-sized apoB-100, and floated mostly between the LDL and HDL density range. It is worth noting that despite the presence of Type II diabetes, both the proband and his father have very low plasma lipid levels and neither have any clinically manifest macrovascular complications. (C) 1998 Elsevier Science Ireland Ltd.