先天性肌营养不良中的POMGnT1、POMT1和POMT2突变。

POMGnT1, POMT1, and POMT2 mutations in congenital muscular dystrophies.

作者信息

Endo Tamao, Manya Hiroshi, Seta Nathalie, Guicheney Pascale

机构信息

Molecular Glycobiology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan.

出版信息

Methods Enzymol. 2010;479:343-52. doi: 10.1016/S0076-6879(10)79019-4.

DOI:10.1016/S0076-6879(10)79019-4

PMID:20816175

Abstract

Alpha-dystroglycanopathies are a group of rare inherited neuromuscular disorders characterized by reduced glycosylation of alpha-dystroglycan (alpha-DG). Mutations in six genes (POMT1, POMT2, POMGNT1, FKTN, FKRP, and LARGE) have been identified in patients with alpha-dystroglycanopathies. Due to an extremely broad clinical spectrum and relatively poor phenotype-genotype correlation, diagnosis of alpha-dystroglycanopathies is difficult and requires searching for mutations gene by gene. At present, of the six proteins involved on alpha-dystroglycanopathies, the function of the gene products is only known for POMT1, POMT2, and POMGnT1, all responsible for the O-mannosylglycan biosynthesis. This chapter describes the assay protocols to diagnose patients with alpha-dystroglycanopathy by measuring glycosyltransferase activity.

摘要

α-肌营养不良糖蛋白病是一组罕见的遗传性神经肌肉疾病，其特征是α-肌营养不良糖蛋白（α-DG）糖基化减少。在α-肌营养不良糖蛋白病患者中已鉴定出六个基因（POMT1、POMT2、POMGNT1、FKTN、FKRP和LARGE）的突变。由于临床谱极广且表型-基因型相关性相对较差，α-肌营养不良糖蛋白病的诊断很困难，需要逐个基因寻找突变。目前，在涉及α-肌营养不良糖蛋白病的六种蛋白质中，仅了解POMT1、POMT2和POMGnT1这三种基因产物的功能，它们均负责O-甘露糖聚糖的生物合成。本章介绍了通过测量糖基转移酶活性来诊断α-肌营养不良糖蛋白病患者的检测方案。