PRNP E200D 纯合突变所致貌似散发性克雅氏病 1 例报告
Case report of homozygous E200D mutation of PRNP in apparently sporadic Creutzfeldt-Jakob disease.
机构信息
Department of Neurology, Leeds General Infirmary, Leeds, LS1 3EX, UK.
MRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
出版信息
BMC Neurol. 2021 Jun 28;21(1):248. doi: 10.1186/s12883-021-02274-w.
BACKGROUND
Inherited prion diseases are rare autosomal dominant disorders associated with diverse clinical presentations. All are associated with mutation of the gene that encodes prion protein (PRNP). Homozygous mutations with atypical clinical phenotypes have been described but are extremely rare.
CASE PRESENTATION
A Chinese patient presented with a rapidly progressive cognitive and motor disorder in the clinical spectrum of sCJD. Investigations strongly suggested a diagnosis of CJD. He was found to carry a homozygous mutation at PRNP codon 200 (E200D), but there was no known family history of the disorder. The estimated allele frequency of E200D in East Asian populations is incompatible with it being a highly penetrant mutation in the heterozygous state.
CONCLUSION
In our view the homozygous PRNP E200D genotype is likely to be causal of CJD in this patient. Homotypic PrP interactions are well known to favour the development of prion disease. The case is compatible with recessively inherited prion disease.
背景
遗传性朊病毒病是罕见的常染色体显性遗传疾病，与多种临床表现相关。所有疾病都与编码朊病毒蛋白（PRNP）的基因突变相关。已有描述携带异常临床表型的纯合突变病例，但极为罕见。
病例报告
一位中国患者出现了 sCJD 临床谱中快速进展的认知和运动障碍。检查强烈提示 CJD 的诊断。他被发现携带 PRNP 密码子 200（E200D）的纯合突变，但该疾病在家族中并无已知病史。E200D 在东亚人群中的估计等位基因频率与杂合状态下的高外显率突变不相符。
结论
我们认为，PRNP E200D 基因型纯合很可能是导致该患者 CJD 的原因。同源型 PrP 相互作用已知有利于朊病毒病的发展。该病例符合隐性遗传朊病毒病。
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