Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, PR China; Department of Radiology, the Third Xiangya Hospital, Central South University, Changsha, PR China.
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, PR China.
Mutat Res Rev Mutat Res. 2018 Oct-Dec;778:45-50. doi: 10.1016/j.mrrev.2018.09.002. Epub 2018 Sep 12.
Protein O-mannosyltransferase 1 (POMT1) is a critical enzyme participating in the first step of protein O-mannosylation. Mutations in the coding gene, POMT1, have been described to be related to a series of autosomal recessive disorders associated with defective alpha-dystroglycan glycosylation, later termed muscular dystrophy-dystroglycanopathies (MDDGs). MDDGs are characterized by a broad phenotypic spectrum of congenital muscular dystrophy or later-onset limb-girdle muscular dystrophy, accompanied by variable degrees of intellectual disability, brain defects, and ocular abnormalities. To date, at least 76 disease-associated mutations in the POMT1 gene, including missense, nonsense, splicing, deletion, insertion/duplication, and insertion-deletion mutations, have been reported in the literature. In this review, we highlight the present knowledge of the identified disease-associated POMT1 gene mutations and genetic animal models related to the POMT1 gene. This review may help further normative classification of phenotypes, assist in definite clinical and genetic diagnoses, and genetic counseling, and may comprehensively improve our understanding of the basis of complex phenotypes and possible pathogenic mechanisms involved.
蛋白-O-甘露糖基转移酶 1（POMT1）是参与蛋白-O-甘露糖化第一步的关键酶。编码基因 POMT1 的突变已被描述与一系列常染色体隐性遗传疾病相关，这些疾病与α- dystroglycan 糖基化缺陷有关，后来被称为肌肉营养不良- dystroglycanopathy（MDDG）。MDDG 的特征是先天性肌肉营养不良或迟发性肢带型肌肉营养不良的广泛表型谱，伴有不同程度的智力障碍、脑缺陷和眼部异常。迄今为止，文献中已经报道了至少 76 种与 POMT1 基因突变相关的疾病，包括错义、无义、剪接、缺失、插入/重复和插入缺失突变。在这篇综述中，我们强调了目前对已识别的与 POMT1 基因突变相关的疾病的了解，以及与 POMT1 基因突变相关的遗传动物模型。这篇综述可能有助于进一步规范表型分类，辅助明确的临床和遗传诊断和遗传咨询，并全面提高我们对复杂表型的基础和可能涉及的致病机制的理解。
