{"id":284,"title":"PLP1-Associated Demyelinating Neuropathy in 2 Female Patients","title_zh":"两例女性PLP1相关脱髓鞘性神经病：成年发病与遗传阻断意义","url":"https://pubmed.ncbi.nlm.nih.gov/42985710","doi":"10.1212/nxg.0000000000200441","pmid":"42985710","journal":"Neurol Genet","kind":"paper","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:04+00:00","authors":["Brito da Silva A","Nicolas Vela M","Lai M","Vico Pardo L","Samaraweera APR","Horvath R","Chinnery PF","Baker MR","Keogh MJ"],"primary_topic":"pgt","topics":[{"slug":"pgt","score":1.0,"hits":["preimplantation genetic"]}],"topic_score":1.0,"preference_score":0.0,"preference_labels":[],"llm_score":56.0,"final_score":56.0,"score_dims":{"novelty":55,"rigor":38,"impact":35,"relevance":45,"translation":45},"recommend_reason":"仅为2例病例报告，证据等级低，且核心内容是成人神经遗传学表型扩展；对ART的价值主要在于提示PLP1可作为PGT-M的候选基因，属于边缘相关信息，可快速浏览。","keywords":["PLP1","脱髓鞘性神经病","痉挛性截瘫","植入前遗传学检测","病例报告"],"selected":0,"story_id":140,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-endo-genetics","source_name":"PubMed · 生殖内分泌/遗传/保存","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该研究报道2例无亲缘关系的女性患者，均经神经传导、肌电图、诱发电位、影像及靶向基因检测确诊携带PLP1致病变异。首例为34岁女性，表现为足下垂，电生理符合以运动为主的脱髓鞘性神经病；第二例为中年女性，携带另一PLP1变异，临床诊断为进行性痉挛性截瘫，电生理显示合并同类脱髓鞘性运动神经病。作者指出，女性PLP1相关疾病可于40–50岁以散发性脱髓鞘运动神经病形式起病，易被误认为获得性免疫介导性神经病，故中年女性散发性病例的基因检测应纳入PLP1；明确诊断有助于获得新兴基因治疗，并可为家系提供植入前遗传学检测以降低子代传播风险。","summary":"OBJECTIVE: The aim of this study was to report 2 unrelated women with demyelinating motor-predominant neuropathy in whom pathogenic variants in the proteolipid protein 1 gene (PLP1) were identified. METHODS: Two unrelated female individuals underwent nerve conduction studies, EMG, evoked potential tests, neuroimaging, and targeted genetic testing. RESULTS: The first patient, a 34-year-old woman, presented with foot drop and had electroneurographic findings consistent with a demyelinating motor-predominant neuropathy, with genetic testing revealing a pathogenic PLP1 variant. The second patient, also middle-aged, had a different pathogenic PLP1 variant and a clinical diagnosis of progressive spastic paraplegia, with detailed electrophysiologic assessment demonstrating a coexistent demyelinating motor-predominant neuropathy. DISCUSSION: These cases demonstrate that PLP1-related disease in women can present in the fourth and fifth decades as a sporadic demyelinating motor-predominant neuropathy, which may be mistaken for an acquired immune-mediated neuropathy. In middle-aged women presenting with an apparently sporadic demyelinating motor neuropathy, genetic testing should, therefore, include PLP1. Recognizing PLP1 disease has important implications, such as access to emerging genetic therapies and the opportunity to offer preimplantation genetic testing to reduce the risk of transmission to offspring.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}