Defective glycosylation in congenital muscular dystrophies
Defective glycosylation in congenital muscular dystrophies
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DOI：
10.1097/00019052-200404000-00020
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发表时间：
2004-04-01
影响因子：
4.8
通讯作者：
Brown, SC
中科院分区：
文献类型：
--
作者：
Muntoni, F;Brockington, M;Brown, SC
综述目的最近发现的5个基因编码的蛋白质与推定或证明糖基转移酶活性的突变揭示了一种新的机制，负责肌营养不良症。α-肌营养不良聚糖的异常糖基化似乎是所有这些病症中的常见发现。令人惊讶的是，由于这些基因中的几个突变引起的疾病严重程度是非常可变的。本文概述了过去一年来在这一领域取得的临床、生化和遗传学进展。最近的发现人类LARGE基因突变，一种假定的糖基转移酶在肌营养不良小鼠中发生突变，现已被鉴定为人类肌营养不良症的一种形式。此外，编码fukutin、蛋白质O-连接甘露糖β 1、2-N-乙酰葡糖胺转移酶1和fukutin相关蛋白的基因突变患者的临床变异性已显著扩大。疾病的严重程度与基因突变的患者编码的福田相关蛋白质的变化从严重的产前形式的先天性肌营养不良症的鹅卵石无脑畸形和结构性眼缺陷，以轻度形式的肢带型肌营养不良症的发病在成年后的生活和既不大脑也不眼睛involved.Summary糖基化疾病代表一个快速增长和常见的一组肌营养不良症。现在可以对五种形式进行准确的基因诊断，预计其他几种变体最终也会属于这些类别。
Purpose of review The recent identification of mutations in five genes coding for proteins with putative or demonstrated glycosyltransferase activity has shed light on a novel mechanism responsible for muscular dystrophy. Abnormal glycosylation of alpha-dystroglycan appears to be a common finding in all these conditions. Surprisingly, the disease severity due to mutations in several of these genes is extremely variable. This article provides an overview of the clinical, biochemical and genetic advances that have been made over the last year in this field.Recent findings Mutations in the human LARGE gene, a putative glycosyltransferase mutated in the myodystrophy mouse, have now been identified in a form of human muscular dystrophy. In addition, the clinical variability of patients with mutations in the genes encoding fukutin, protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 and the fukutin-related protein has been significantly expanded. Disease severity in patients with mutations in the gene encoding the fukutin-related protein varies from a severe prenatal form of congenital muscular dystrophy with cobblestone lissencephaly and structural eye defects to a mild form of limb-girdle muscular dystrophy with onset in adult life and neither brain nor eye involvement.Summary Glycosylation disorders represent a rapidly growing and common group of muscular dystrophies. Accurate genetic diagnosis can now be made for five forms, and it is anticipated that several other variants will eventually fall into these categories.