Mastrianni J A, Curtis M T, Oberholtzer J C, Da Costa M M, DeArmond S, Prusiner S B, Garbern J Y
Department of Neurology, University of California, San Francisco 94143-0518, USA.
Neurology. 1995 Nov;45(11):2042-50. doi: 10.1212/wnl.45.11.2042.
Gerstmann-Sträussler-Scheinker disease (GSS) is caused by several different point mutations of the prion protein (PrP) gene, each of which generally produces a distinct clinical phenotype. An ataxic form of GSS is genetically linked to a mutation at codon 102 (CCG-->CTG) leading to the substitution of leucine for proline, while a "telencephalic" variant of GSS, in which dementia is the predominant symptom and ataxia is minimal, has been described in two kindreds with a mutation at codon 117 (GCA-->GTG) resulting in the substitution of valine for alanine. In this report, we present a family with ataxic GSS that has, however, the same mutation at codon 117 as is present in the telencephalic variant of GSS. Other than an additional silent mutation (GCA-->GCG) at codon 117 on the normal allele, there were no other mutations detected. At the polymorphic codon 129, valine was encoded by both alleles in the proband that we studied. Why this family with prion disease (PrP-A117V) should present with ataxia instead of dementia, which was found in two previously identified families with the same PrP gene mutation, remains to be established.
格斯特曼-施特劳斯勒-申克病（GSS）由朊蛋白（PrP）基因的几种不同点突变引起，每种突变通常产生独特的临床表型。GSS的共济失调型在基因上与密码子102处的突变（CCG→CTG）相关，导致脯氨酸被亮氨酸取代，而GSS的一种“端脑”变体，其中痴呆是主要症状且共济失调轻微，在两个家系中被描述，其密码子117处有突变（GCA→GTG）导致丙氨酸被缬氨酸取代。在本报告中，我们展示了一个患有共济失调型GSS的家系，然而，该家系在密码子117处的突变与GSS端脑变体中的突变相同。除了正常等位基因上密码子117处的一个额外沉默突变（GCA→GCG）外，未检测到其他突变。在我们研究的先证者中，两个等位基因在多态密码子129处均编码缬氨酸。为什么这个患有朊病毒病（PrP-A117V）的家系表现为共济失调而不是痴呆，而在之前鉴定的两个具有相同PrP基因突变的家系中发现的是痴呆，仍有待确定。
