Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Schwabachanlage 10, Erlangen, Germany.
Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):131-42. doi: 10.1016/j.beem.2010.08.004.
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.
软骨毛发发育不良和矮小性发育不良是两种常染色体隐性骨骼发育不良，其特点是干骺端到脊椎-骺端-骺板发育不良的程度不同，并有不同程度的其他附加特征，包括易患癌症、贫血、免疫缺陷、胃肠道吸收不良和先天性巨结肠。这两种疾病都是由未翻译的 RMRP 基因突变引起的，该基因形成了 RNase MRP 复合物的 RNA 亚单位。该复合物通过切割 5.8S rRNA 参与核糖体组装，通过有丝分裂末期 Cyclin B2 mRNA 的切割控制细胞周期，处理线粒体 RNA，并与 hTERT 形成复合物，提示可能参与 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 mRNA 切割活性显著降低是免疫缺陷的前提。因此，在大多数情况下，临床表型是由于对各自对 RNase MRP 功能的影响的综合作用而出现的。
