Identification and functional study of novel PLP1 mutations in Chinese patients with Pelizaeus-Merzbacher disease
Identification and functional study of novel PLP1 mutations in Chinese patients with Pelizaeus-Merzbacher disease
复制标题
中国Pelizaeus-Merzbacher病患者PLP1新突变的鉴定及功能研究
DOI：
10.1016/j.braindev.2014.11.007
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发表时间：
2015-09-01
影响因子：
1.7
通讯作者：
Jiang, Yuwu
中科院分区：
文献类型：
--
作者：
Xie, Han;Feng, Hongchun;Jiang, Yuwu
目的：Pelizaeus-Merzbacher病(PMD)是一种罕见的X连锁隐性髓鞘减退疾病，以眼球震颤、共济失调、运动发育障碍和进行性痉挛为特征。本研究的目的是对中国人Pelizaeus-Merzbacher病(PMD)患者的蛋白脂蛋白1(PLP1)突变进行鉴定，并确认已鉴定突变的生物学影响。方法：对PMD患者的临床资料进行分析和随访研究。结果：在7例男性PMD患者中检测到PLP1基因突变。在7例中国PMD患者中发现了3个新的PLP1错义突变(c.353C>；G，p.T118R；c.623G>；T，p.G208V；c.709T>；G，p.F237V)和3个已报道的错义突变(c.467C>；T，p.T156I；c.517C>；T，p.P173S；c.646C>；T，p.P2165)。3个突变(例2为F237V，例5为P216S，例6为T156I)是新发现的。结论：我们鉴定出6种致病突变，丰富了PMD患者错义突变的特异性谱。这六个PLP1突变可能是致病的。通过回顾已知的PLP1突变，我们初步揭示了错义突变的位置可能与PMD的严重程度有关。(C)2014年日本儿童神经病学学会。爱思唯尔出版，版权所有。
Purpose: Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive hypomyelination disorder characterized by nystagmus, ataxia, impaired motor development, and progressive spasticity. Identification of proteolipid protein 1 (PLP1) mutations in Chinese patients with Pelizaeus-Merzbacher disease (PMD) and confirmation of the biological impacts of the identified mutations are the aims of this study.Methods: An analysis of clinical materials and a follow-up study were conducted for the patients with PMD. Sequencing and immunofluorescence were applied for molecular analysis of the causative gene PLP1.Results: We identified PLP1 mutations in seven male patients with PMD. Three novel missense mutations (c.353C>G, p.T118R; c.623G>T, p.G208V; c.709T>G, p.F237V) and three reported missense mutations (c.467C>T, p.T156I; c.517C>T, p.P173S; c.646C>T, p.P2165) of PLP1 were identified from seven Chinese PMD patients. The three mutations (F237V in patient 2, P216S in patient 5 and T156I in patient 6) were de novo. Mutant proteins were trapped in the lumen of endoplasmic reticulum.Conclusion: We have identified six pathogenic mutations, enriching the specific spectrum of missense mutations in the patients with PMD. The six PLP1 mutations are probably pathogenic. By reviewing the known PLP1 mutations, we have preliminarily revealed the position of missense mutation may be associated with the severity of PMD. (C) 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.