Notarangelo Luigi D, Roifman Chaim M, Giliani Silvia
Division of Immunology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Curr Opin Allergy Clin Immunol. 2008 Dec;8(6):534-9. doi: 10.1097/ACI.0b013e328310fe7d.
To report on the expanding clinical and immunological spectrum associated with ribonuclease mitochondrial RNA-processing mutations and to review the cellular and molecular mechanisms involved in the pathophysiology of cartilage-hair hypoplasia (CHH) and related disorders in humans.
Different types of mutations are associated with skeletal or extraskeletal manifestations of CHH, respectively. In particular, severe immunodeficiency is mostly associated with mutations that alter cyclin B2 mRNA cleavage and thus are likely to reflect disturbances in cell cycle control. The first cases of ribonuclease mitochondrial RNA-processing mutations with severe immunodeficiency, but no skeletal abnormalities, have been identified.
Abnormalities of ribosome biogenesis have been shown to cause distinct bone marrow failure syndromes, including CHH. However, the specific role of ribosomal and extraribosomal defects in the pathophysiology of the various phenotypic features of CHH remains undefined. Development of suitable animal models is needed to address this important issue.
报告与核糖核酸酶线粒体RNA加工突变相关的不断扩展的临床和免疫谱，并综述人类软骨毛发发育不全（CHH）及相关疾病病理生理学中涉及的细胞和分子机制。
不同类型的突变分别与CHH的骨骼或骨骼外表现相关。特别是，严重免疫缺陷大多与改变细胞周期蛋白B2 mRNA切割的突变相关，因此可能反映细胞周期控制的紊乱。已鉴定出首例具有严重免疫缺陷但无骨骼异常的核糖核酸酶线粒体RNA加工突变病例。
核糖体生物合成异常已被证明可导致包括CHH在内的不同骨髓衰竭综合征。然而，核糖体和核糖体外缺陷在CHH各种表型特征病理生理学中的具体作用仍不明确。需要开发合适的动物模型来解决这一重要问题。
