The PLP1 gene, located on chromosome Xq22, encodes the proteolipid protein 1 and its isoform DM20. Mutations in PLP1 cause a spectrum of white matter disorders of variable severity. Here we report on four additional HEMS patients from three families harboring three novel PLP1 mutations in exon 3B detected by targeted next-generation sequencing. Patients experienced psychomotor delay or nystagmus in the first year of age and then developed ataxic–spastic or ataxic syndrome, compatible with a phenotype of intermediate severity in the spectrum of PLP1-related disorders. Regression occurred at the beginning of the third decade of the eldest patient. Extrapyramidal involvement was rarely observed. Brain MRI confirmed the involvement of structures that physiologically myelinate early, although the pattern of abnormalities may differ depending on the age at which the study is performed. These new cases contribute to expanding the phenotypic and genotypic spectrum of HEMS. Additional studies, especially enriched by systematic functional evaluations and long-term follow-up, are welcome to better delineate the natural history of this rare hypomyelinating leukodystrophy.

中文翻译：

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扩大早期有髓结构（HEMS）的PLP1相关性髓鞘质变的临床和突变谱

位于染色体Xq22上的PLP1基因编码蛋白脂蛋白1及其同工型DM20。PLP1中的突变会导致一系列严重程度不同的白质疾病。在这里，我们报告了来自三个家庭的另外四个HEMS患者，这些患者在靶向的下一代测序中检测到外显子3B中存在三个新的PLP1突变。患者在第一岁时经历了精神运动性延迟或眼球震颤，然后发展为共济失调-痉挛或共济失调综合征，与PLP1频谱中度严重程度的表型兼容相关疾病。退化发生在年龄最大的患者的第三个十年开始时。很少发生锥体外系受累。脑部MRI证实了早期生理上发生髓鞘形成的结构的参与，尽管异常的模式可能因研究的年龄而异。这些新病例有助于扩大HEMS的表型和基因型谱。欢迎进行更多的研究，尤其是通过系统的功能评估和长期的跟踪研究，以更好地描绘这种罕见的髓鞘性白细胞营养不良的自然史。