Shimojima Keiko, Okumura Akihisa, Ikeno Mitsuru, Nishimura Akira, Saito Akira, Saitsu Hirotomo, Matsumoto Naomichi, Yamamoto Toshiyuki
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan; Department of Pediatrics, Aichi Medical University, Nagakute, Japan.
Brain Dev. 2015 Mar;37(3):281-5. doi: 10.1016/j.braindev.2014.05.004. Epub 2014 Jun 26.
Hypomyelinating leukoencephalopathy is a heterogeneous disorder caused by mutations in several-different genes. Clinical entity of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is one of them.
A male patient showed pendular nystagmus, infantile hypotonia, an abnormal pattern of brain auditory evoked potential, and hypomyelination on brain magnetic resonance imaging, which suggested Pelizaeus-Merzbacher disease (PMD) as the candidate diagnosis; however, no abnormality was found in the proteolipid protein 1 gene (PLP1) that is responsible for PMD. Whole exome sequencing was performed to identify pathogenic mutations in this patient.
A de novo mutation was identified in the tubulin 4a gene (TUBB4A), which has been recently reported to be associated with H-ABC. Although the patient did not show any neurological features suggesting H-ABC, such as extrapyramidal or cerebellar signs, radiological findings demonstrated the finding of cerebellar atrophy at the age of 36months.
This study suggested us the difficulty of clinical diagnosis for H-ABC early in the life of the patient, which makes predication of prognosis and genetic counseling difficult.
低髓鞘性白质脑病是一种由多种不同基因突变引起的异质性疾病。基底节和小脑萎缩性低髓鞘症（H-ABC）的临床实体是其中之一。
一名男性患者表现出钟摆样眼球震颤、婴儿期肌张力减退、脑听觉诱发电位异常模式以及脑磁共振成像显示低髓鞘，提示可能诊断为佩利措伊斯-梅茨巴赫病（PMD）；然而，负责PMD的蛋白脂蛋白1基因（PLP1）未发现异常。对该患者进行了全外显子组测序以鉴定致病突变。
在微管蛋白4a基因（TUBB4A）中鉴定出一个新发突变，该基因最近已被报道与H-ABC相关。尽管该患者未表现出任何提示H-ABC的神经学特征，如锥体外系或小脑体征，但影像学检查结果显示在36个月龄时发现小脑萎缩。
本研究提示我们，在患者生命早期对H-ABC进行临床诊断存在困难，这使得预后预测和遗传咨询变得困难。
