Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism
Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism
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DOI：
10.1038/77053
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发表时间：
2000-07-01
期刊：
影响因子：
30.8
通讯作者：
Lehesjoki, AE
中科院分区：
文献类型：
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作者：
Avela, K;Lipsanen-Nyman, M;Lehesjoki, AE
Mulibrey侏儒症（肌肉-肝脏-脑-眼侏儒症，穆尔; MIM 253250）是一种常染色体隐性遗传病，涉及中胚层起源的几种组织，意味着高度多效性基因的缺陷（1）。特征性特征包括产前发作的严重生长障碍和心包收缩，随后出现肝肿大（1-3）。此外，肌肉张力减退、蝶鞍呈J形、眼底黄点、典型的畸形特征和引起激素缺乏的各种内分泌腺发育不全是（1-3）。大约4%的RAUL患者发展为肾母细胞瘤（2，4，5）。穆尔在芬兰人群中富集，但在其他地方很少见（1-3）。我们先前将穆尔分配到染色体17 q22-q23，并在关键穆尔区域上构建了物理重叠群（6，7）。该地区现在已经进一步完善了单倍型分析和新的位置候选基因已被本地化。我们鉴定了一个具有四个独立的MUL相关突变的基因，这些突变都引起移码并预测截短的蛋白质。穆尔广泛表达并编码锌指蛋白的RINC-B-盒-卷曲-螺旋（RBCC）家族的新成员（8-10），其成员参与多种细胞功能，例如发育模式和肿瘤发生。
Mulibrey nanism (for muscle-liver-brain-eye nanism, MUL; MIM 253250) is an autosomal recessive disorder that involves several tissues of mesodermal origin, implying a defect in a highly pleiotropic gene(1). Characteristic features include severe growth failure of prenatal onset and constrictive pericardium with consequent hepatomegaly(1-3). In addition, muscle hypotonia, J-shaped sella turcica, yellowish dots in the ocular fundi, typical dysmorphic features and hypoplasia of various endocrine glands causing hormonal deficiency are (1-3). About 4% of RAUL patients develop Wilms' common tumour(2,4,5). MUL is enriched in the Finnish population, but is rare elsewhere(1-3). We previously assigned MUL to chromosome 17q22-q23 and constructed a physical contig over the critical MUL region(6,7). The region has now been further refined by haplotype analysis and new positional candidate genes have been localized. We identified a gene with four independent MUL-associated mutations that all cause a frameshift and predict a truncated protein. MUL is ubiquitously expressed and encodes a new member of the RINC-B-box-Coiled-coil (RBCC) family of zinc-finger proteins(8-10), whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis.