The molecular basis of the cartilage-hair hypoplasia-anauxetic dysplasia spectrum
The molecular basis of the cartilage-hair hypoplasia-anauxetic dysplasia spectrum
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DOI：
10.1016/j.beem.2010.08.004
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发表时间：
2011-02-01
影响因子：
7.4
通讯作者：
Rauch, Anita
中科院分区：
文献类型：
--
作者：
Thiel, Christian T.;Rauch, Anita
软骨-毛发发育不全和发育不良是两种常染色体隐性遗传的骨骼发育不良，其特征在于从干骺端到脊椎-间-骺发育不良的不同程度和可变的附加特征，包括癌症易感性、贫血、免疫缺陷、胃肠道吸收不良和先天性巨结肠。两者都是由非翻译的RMRP基因突变引起的，该基因形成了RNase MRP复合物的RNA亚基。该复合物通过切割5.8S rRNA参与核糖体组装，通过在有丝分裂结束时切割细胞周期蛋白B2 mRNA控制细胞周期，加工线粒体RNA，并与hTERT形成复合物，表明可能参与siRNA合成的表达调控。骨骼发育不良的程度主要与rRNA切割活性相关，而显著降低的mRNA切割活性是免疫缺陷的先决条件。因此，在大多数情况下，临床表型出现了对RNase MRP功能的各自作用的组合效应。(C)2010爱思唯尔有限公司版权所有。
Cartilage-hair hypoplasia and anauxetic dysplasia are two autosomal recessive skeletal dysplasias characterized by different degrees from metaphyseal to spondylo-meta-epiphyseal dysplasia and variable additional features including predisposition to cancer, anemia, immunodeficiency, and gastrointestinal malabsorption and Hirschsprung's disease. Both are caused by mutations in the untranslated RMRP gene, which forms the RNA subunit of the RNase MRP complex. This complex is involved in the ribosome assembly by cleavage of 5.8S rRNA, cell cycle control by Cyclin B2 mRNA cleavage at the end of mitosis, processing the mitochondrial RNA, and forming a complex with hTERT suggesting a possible involvement in expression regulation by siRNA synthesis. The degree of skeletal dysplasia correlates mainly with the rRNA cleavage activity, whereas significantly diminished mRNA cleavage activity is a prerequisite for immunodeficiency. Thus, the clinical phenotype emerges in most cases of the combined effect on the respective effect on RNase MRP function. (C) 2010 Elsevier Ltd. All rights reserved.