Small de novo duplication in the repeat region of the TATA‐box‐binding protein gene manifest with a phenotype similar to variant Creutzfeldt‐Jakob disease
Small de novo duplication in the repeat region of the TATA‐box‐binding protein gene manifest with a phenotype similar to variant Creutzfeldt‐Jakob disease
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DOI：
10.1111/j.1399-0004.2004.00356.x
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发表时间：
2004-12
影响因子：
3.5
通讯作者：
A. Shatunov;Esteban A. Fridman;FI Pagan;J. Leib;Andrew B. Singleton;M. Hallett;L. Goldfarb
中科院分区：
文献类型：
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作者：
A. Shatunov;Esteban A. Fridman;FI Pagan;J. Leib;Andrew B. Singleton;M. Hallett;L. Goldfarb
一名20岁的北美患者发生了快速进行性认知功能下降和明显的共济失调，这是一种与朊病毒病相容的表型。在PRNP基因中没有发现结构变化，排除了遗传性朊病毒病，但已知患者的PRNP密码子129 Met/Met基因型易患变异型克雅氏病（vCJD）。进一步的研究确定了一个扩展的等位基因与55 CAG/CAA重复的TBP基因。TBP基因编码区三核苷酸重复数的增加与脊髓小脑性共济失调17型（SCA 17）有关。患者未受影响的父母和兄弟姐妹显示正常大小的TBP等位基因，具有37-38个重复。单倍型和核苷酸序列分析清楚地表明，突变已发生从头父染色体上的插入/复制（CAA）（CAG）（CAA）（CAG）15序列。这份报告提出了第二个充分调查的SCA 17发生作为一个多态性TBP三核苷酸重复区域内的DNA重排的结果散发病例。我们的研究结果表明，疑似vCJD的患者应接受SCA 17、亨廷顿病和其他与vCJD具有表型相似性的神经变性疾病的检测。
A 20‐year‐old North American patient developed rapidly progressive cognitive decline and pronounced ataxia, a phenotype compatible with prion disease. No structural changes were found in the PRNP gene, which excludes genetic prion disease, but the patient's PRNP codon 129 Met/Met genotype is known to predispose to variant Creutzfeldt‐Jakob disease (vCJD). Further studies identified an expanded allele with 55 CAG/CAA repeats in the TBP gene. The increase of trinucleotide repeat number in the coding region of the TBP gene has previously been associated with spinocerebellar ataxia type 17 (SCA17). The patient's unaffected parents and siblings show normal‐size TBP alleles with 37–38 repeats. Haplotype and nucleotide sequence analyses clearly indicate that the mutation has occurred de novo on a paternal chromosome by insertion/duplication of a (CAA)(CAG)(CAA)(CAG)15 sequence. This report presents a second fully investigated sporadic case of SCA17 occurring as a result of a DNA rearrangement within the polymorphic TBP trinucleotide repeat region. Our findings suggest that patients suspected of vCJD should undergo testing for SCA17, Huntington's disease and other neurodegener‐ative disorders having phenotypic similarities with vCJD.