PDF(Pubmed)
Abstract：
BACKGROUND: Genetic prion diseases, including Gerstmann-Sträussler-Scheinker disease (GSS), are extremely rare, fatal neurodegenerative disorders, often associated with progressive ataxia and cognitive/neuropsychiatric symptoms. GSS typically presents as a rapidly progressive cerebellar ataxia, associated with cognitive decline. Late-onset cases are rare.
OBJECTIVE: To compare a novel GSS phenotype with six other cases and present pathological findings from a single case.
METHODS: Case series of seven GSS patients, one proceeding to autopsy.
RESULTS: Case 1 developed slowly progressive gait difficulties at age 71, mimicking a spinocerebellar ataxia, with a family history of balance problems in old age. Genome sequencing revealed a heterozygous c.392G > A (p.G131E) pathogenic variant and a c.395A > G resulting in p.129 M/V polymorphism in the PRNP gene. Probability analyses considering family history, phenotype, and a similar previously reported point mutation (p.G131V) suggest p.G131E as a new pathogenic variant. Clinical features and imaging of this case are compared with those six additional cases harboring p.P102L mutations. Autopsy findings of a case are described and were consistent with the prion pathology of GSS.
CONCLUSIONS: We describe a patient with GSS with a novel p.G131E mutation in the PRNP gene, presenting with a late-onset, slowly progressive phenotype, mimicking a spinocerebellar ataxia, and six additional cases with the typical P102L mutation.
OBJECTIVE: To compare a novel GSS phenotype with six other cases and present pathological findings from a single case.
METHODS: Case series of seven GSS patients, one proceeding to autopsy.
RESULTS: Case 1 developed slowly progressive gait difficulties at age 71, mimicking a spinocerebellar ataxia, with a family history of balance problems in old age. Genome sequencing revealed a heterozygous c.392G > A (p.G131E) pathogenic variant and a c.395A > G resulting in p.129 M/V polymorphism in the PRNP gene. Probability analyses considering family history, phenotype, and a similar previously reported point mutation (p.G131V) suggest p.G131E as a new pathogenic variant. Clinical features and imaging of this case are compared with those six additional cases harboring p.P102L mutations. Autopsy findings of a case are described and were consistent with the prion pathology of GSS.
CONCLUSIONS: We describe a patient with GSS with a novel p.G131E mutation in the PRNP gene, presenting with a late-onset, slowly progressive phenotype, mimicking a spinocerebellar ataxia, and six additional cases with the typical P102L mutation.
摘要：
背景：遗传性朊病毒病，包括Gerstmann-Sträussler-Scheinker病（GSS），非常罕见，致命的神经退行性疾病，常伴有进行性共济失调和认知/神经精神症状。GSS通常表现为快速进行性小脑共济失调，与认知能力下降有关。迟发性病例很少见。
目的：将一种新的GSS表型与其他6例病例进行比较，并提供单个病例的病理结果。
方法：7名GSS患者的病例系列，一个正在进行尸检。
结果：病例1在71岁时出现缓慢进行性步态困难，模仿脊髓小脑共济失调，有老年平衡问题的家族史。基因组测序显示杂合c.392G>A（p。G131E）致病性变体和c.395A>G，导致PRNP基因中的p.129M/V多态性。考虑家族史的概率分析，表型,和先前报道的类似点突变（p。G131V)提示p.G131E是一种新的致病变异体。将该病例的临床特征和影像学与另外6例具有p.P102L突变的病例进行了比较。描述了一个病例的尸检结果，与GSS的朊病毒病理学一致。
结论：我们描述了一名患有GSS的患者，在PRNP基因中有一个新的p.G131E突变，呈现迟发性，缓慢进展的表型，模仿脊髓小脑共济失调，以及另外6例具有典型P102L突变的病例。
目的：将一种新的GSS表型与其他6例病例进行比较，并提供单个病例的病理结果。
方法：7名GSS患者的病例系列，一个正在进行尸检。
结果：病例1在71岁时出现缓慢进行性步态困难，模仿脊髓小脑共济失调，有老年平衡问题的家族史。基因组测序显示杂合c.392G>A（p。G131E）致病性变体和c.395A>G，导致PRNP基因中的p.129M/V多态性。考虑家族史的概率分析，表型,和先前报道的类似点突变（p。G131V)提示p.G131E是一种新的致病变异体。将该病例的临床特征和影像学与另外6例具有p.P102L突变的病例进行了比较。描述了一个病例的尸检结果，与GSS的朊病毒病理学一致。
结论：我们描述了一名患有GSS的患者，在PRNP基因中有一个新的p.G131E突变，呈现迟发性，缓慢进展的表型，模仿脊髓小脑共济失调，以及另外6例具有典型P102L突变的病例。
