Identification of DPAGT1 as a new gene in which mutations cause a congenital myasthenic syndrome.
Identification of DPAGT1 as a new gene in which mutations cause a congenital myasthenic syndrome.
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DOI：
10.1111/j.1749-6632.2012.06790.x
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发表时间：
2012-12
影响因子：
5.2
通讯作者：
Beeson D
中科院分区：
文献类型：
--
作者：
Belaya K;Finlayson S;Cossins J;Liu WW;Maxwell S;Palace J;Beeson D
先天性肌无力综合征(CMS)是一组遗传性疾病，由神经肌肉突触的信号传递受损引起。他们的特点是疲劳性肌肉无力。这是一组异质性的疾病，有15个不同的基因与疾病的发展有关。通过外显子全序列测定，我们发现DPAGT1是一个与CMS相关的新基因。DPAGT1催化N-连接蛋白糖基化的第一步。DPAGT1患者的特点是四肢肌肉无力，对胆碱酯酶抑制剂的治疗有反应，肌肉活检中出现管状聚集物。我们发现，DPAGT1是乙酰胆碱受体(AChR)亚单位糖基化和AChR有效输出到细胞表面所必需的。我们认为DPAGT1相关CMS的主要致病机制是终板区AChRs水平降低。这一发现表明，N-连接的糖基化途径的损害可以导致CMS的发展。
Congenital myasthenic syndromes (CMS) are a group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle weakness. This is a heterogenous group of disorders with 15 different genes implicated in the development of the disease. Using whole-exome sequencing we identified DPAGT1 as a new gene associated with CMS. DPAGT1 catalyses the first step of N-linked protein glycosylation. DPAGT1 patients are characterized by weakness of limb muscles, response to treatment with cholinesterase inhibitors, and the presence of tubular aggregates on muscle biopsy. We showed that DPAGT1 is required for glycosylation of acetylcholine receptor (AChR) subunits and efficient export of AChR to the cell surface. We suggest that the primary pathogenic mechanism of DPAGT1-associated CMS is reduced levels of AChRs at the endplate region. This finding demonstrates that impairment of the N-linked glycosylation pathway can lead to the development of CMS.
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DOI：
10.1016/0169-328x(91)90016-q
发表时间：
1991-08-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
GEHLE, VM;SUMIKAWA, K
通讯作者：
SUMIKAWA, K
影响因子：
2.9
作者：
Larkin A;Imperiali B
通讯作者：
Imperiali B
影响因子：
2
作者：
Arroyo Carrera, Ignacio;Matthijs, Gert;Perez Cerda, Celia
通讯作者：
Perez Cerda, Celia
影响因子：
5.8
作者：
Beitz, E
通讯作者：
Beitz, E
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.