PDF(Pubmed)
Abstract：
Infantile onset transient hypomyelination (IOTH) is a rare form of leukodystrophy that is associated with transient motor impairment and delayed central nervous system myelination. Here, we report a case of a new mutation in the transmembrane protein 63A (TMEM63A) gene identified using Whole-Exome Sequencing (WES) in an 8.5-year-old boy with clinical symptoms similar to IOTH. The patient exhibited a mild developmental delay, including hypotonia and delayed motor milestones, as well as some notable phenotypic characteristics, such as macrocephaly and macrosomia. Despite the absence of early neuroimaging, genetic testing revealed a paternally inherited variant in TMEM63A (NM_14698.3:c.220A>T;p:(Arg74*)), potentially linked to infantile transient hypomyelinating leukodystrophy type 19. Our findings in this study and the patient\'s favorable clinical course underscore the potential for successful myelination even with delayed initiation and may contribute to a better understanding of the genotype-phenotype correlation in IOTH, emphasizing the importance of genetic analysis in unresolved developmental delay cases and providing critical insights for accurate diagnosis, prognosis and potential therapeutic strategies in rare leukodystrophies.
摘要：
婴儿发作性短暂性髓鞘减少（IOTH）是一种罕见的脑白质营养不良，与短暂性运动障碍和中枢神经系统髓鞘形成延迟有关。这里,我们报道了一例使用全外显子组测序(WES)在临床症状与IOTH相似的8.5岁男孩中鉴定的跨膜蛋白63A(TMEM63A)基因发生新突变的病例.患者表现出轻微的发育迟缓，包括张力过低和延迟运动里程碑，以及一些显著的表型特征，比如大头畸形和巨大儿。尽管没有早期神经成像，遗传检测揭示了TMEM63A的父系遗传变体（NM_14698.3：c.220A>T；p：（Arg74*）），可能与婴儿短暂性髓鞘减少19型脑白质营养不良有关。我们在这项研究中的发现和患者的有利的临床过程强调了成功的髓鞘形成的潜力，即使延迟启动，可能有助于更好地理解基因型-表型相关性在IOTH，强调遗传分析在未解决的发育延迟病例中的重要性，并为准确诊断提供关键见解，罕见脑白质营养不良的预后和潜在治疗策略.
