Approaches to diagnostic screening for congenital disorders of glycosylation and its prevalence in Japan.

IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY
Nobuhiko Okamoto, Machiko Kadoya, Yoshinao Wada
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引用次数: 0

Abstract

Congenital disorders of glycosylation (CDG) represent an emerging and significant category within the spectrum of inborn errors of metabolism. CDG comprise a heterogeneous group of diseases caused by defects at various stages of the glycosylation pathway. Each year, new types of CDG are identified, and to date, pathogenic variants in 189 genes have been associated with over 200 distinct human glycosylation-related disorders. Each type of CDG exhibits characteristic clinical features. Many of CDG result in multisystem involvement, with the central nervous system being particularly affected. Clinical manifestations are highly variable and may include developmental delays, growth impairment, neurological abnormalities such as ataxia, hepatic dysfunction, cardiac defects, coagulation disorders, and abnormal fat distribution. In patients with unexplained neurological symptoms, it is now standard practice to include CDG in the differential diagnosis. Detection of altered glycosylation patterns in serum proteins is essential in the diagnostic evaluation of CDG. Analytical techniques allow the identification of defects in N-glycosylation, O-glycosylation, and combined glycosylation pathways. Once abnormalities in glycosylation are detected, subsequent genetic analysis is necessary to identify causative variants. Our research institute has contributed to the CDG diagnostic support center in Japan by developing novel analytical methods utilizing mass spectrometry. Through these efforts, we have facilitated the molecular diagnosis of 66 patients with CDG across Japan. In this report, we provide an overview of the current landscape of CDG in Japan, along with a summary of the screening and diagnostic processes.

先天性糖基化疾病的诊断筛选方法及其在日本的患病率。
先天性糖基化障碍(CDG)代表了一个新兴的和显著的类别内的频谱的先天性代谢错误。CDG包括由糖基化途径不同阶段的缺陷引起的异质组疾病。每年都会发现新的CDG类型,迄今为止,189个基因的致病性变异已与200多种不同的人类糖基化相关疾病相关。每种类型的CDG都有其独特的临床特征。许多CDG导致多系统受累,特别是中枢神经系统受到影响。临床表现千差万别,可能包括发育迟缓、生长障碍、共济失调等神经系统异常、肝功能障碍、心脏缺陷、凝血功能障碍和脂肪分布异常。对于有无法解释的神经系统症状的患者,将CDG纳入鉴别诊断是目前的标准做法。检测血清蛋白糖基化模式的改变在CDG的诊断评价中是必不可少的。分析技术允许鉴定n -糖基化,o -糖基化和组合糖基化途径中的缺陷。一旦检测到糖基化异常,随后的遗传分析是必要的,以确定致病变异。我们的研究所通过开发新的质谱分析方法,为日本CDG诊断支持中心做出了贡献。通过这些努力,我们已经促进了日本66名CDG患者的分子诊断。在本报告中,我们概述了日本CDG的现状,并总结了筛查和诊断过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Human Genetics
Journal of Human Genetics 生物-遗传学
CiteScore
7.20
自引率
0.00%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy. Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.
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