The mutation spectrum of the bestrophin protein - functional implications
The mutation spectrum of the bestrophin protein - functional implications
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DOI：
10.1007/s004390050972
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发表时间：
1999-05-01
期刊：
影响因子：
5.3
通讯作者：
Wadelius, C
中科院分区：
文献类型：
--
作者：
Bakall, B;Marknell, T;Wadelius, C
贝斯特黄斑营养不良（BMD），也称为卵黄状黄斑变性2型（VMD 2; OMIM 153700），是一种常染色体显性形式的黄斑变性，主要在青少年发病。BMD的特征在于视网膜色素上皮内和下方的脂褐素的积累。通过重组断点定位，导致该疾病的基因已定位于11 q13。最近，我们已经确定了致病基因编码的蛋白质命名为bestrophin，和突变已被发现主要影响的残基，从一个家庭的基因在秀丽隐杆线虫保守。到目前为止，雌激素的功能尚不清楚，并且无法通过序列比较做出可靠的预测。我们调查了14个无关的瑞典，荷兰，丹麦和摩洛哥的BMD受影响的家庭中的bestrophin基因，发现了8个新的突变。包括以前发表的突变，15个不同的错义突变，现在已被检测到在19的22个家庭与BMD由我们的实验室调查。有趣的是，突变聚集在某些区域，并且没有发现无义突变或引起移码的突变。脑啡肽蛋白的结构元件的计算机模拟表明，这种蛋白质可能是膜结合的，具有四个假定的跨膜区域。
Best's macular dystrophy (BMD), also known as vitelliform macular degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of macular degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans. The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.