Clinical and genetic characterization of a 2-year-old boy with complete PLP1 deletion
Clinical and genetic characterization of a 2-year-old boy with complete PLP1 deletion
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DOI：
10.1016/j.braindev.2012.02.006
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发表时间：
2012-11-01
影响因子：
1.7
通讯作者：
Hara, Toshiro
中科院分区：
文献类型：
--
作者：
Torisu, Hiroyuki;Iwaki, Akiko;Hara, Toshiro
我们在此报告一例2岁男孩诊断为轻度形式的Pelizaeus Merzbacher病由于整个蛋白脂质蛋白1（PLP 1）基因缺失。患者表现为痉挛性四肢瘫痪、智力迟钝和小头畸形。他表现出脑干听觉诱发电位，峰间潜伏期延长，磁共振成像特征提示除脑干、小脑脚、胼胝体和内囊后肢外，大脑大部分区域髓鞘形成不足。质子磁共振波谱显示轻度降低的N-乙酰天冬氨酸肌酸水平的比例在白色的问题，这表明轴突参与。此外，下肢神经传导速度轻度降低。基因分析显示该患者PLP 1缺失。进一步的基因组作图以及缺失断点的序列分析显示，长度约73 kb的基因组区域（包括整个PLP 1和RAB 9 B）被缺失。该缺失的大小是以前在该地区报道的最小的。除了1个碱基对的微同源性外，在远端和近端断点周围的区域之间没有同源序列，这表明缺失是通过非同源末端连接发生的。(C)2012年日本儿童神经病学学会。Elsevier B. V.出版，保留所有权利。
We report herein a case of 2-year-old boy diagnosed with a mild form of Pelizaeus Merzbacher disease due to deletion of the entire proteolipid protein 1 (PLP1) gene. The patient demonstrated spastic quadriplegia, mental retardation, and microcephaly. He exhibited brainstem auditory evoked potentials with prolonged interpeak latencies and magnetic resonance imaging characteristics suggestive of hypomyelination in most areas of the brain with the exception of the brainstem, cerebellar peduncles, corpus callosum, and the posterior limbs of the internal capsules. Proton magnetic resonance spectroscopy revealed a mildly reduced ratio of N-acetyl aspartate to creatine levels in the white matter, suggesting axonal involvement. Additionally, nerve conduction velocity of the lower extremities was mildly decreased. Genetic analysis showed a deletion of PLP1 in this patient. Further genome mapping followed by sequence analysis of the deletion breakpoints revealed that a genomic region, about 73 kb in length, including the entire PLP1 and RAB9B, was deleted. The size of the deletion was the smallest among those previously reported in this region. Except for the 1-base pair microhomology, there were no homologous sequences between the regions around the distal and proximal breakpoints, which suggests that the deletion occurred by nonhomologous end joining. (C) 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.