Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias.
Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias.
复制标题
筛选常染色体显性小脑共济失调中具有多聚谷氨酰胺扩展的蛋白质。
作者：
G. Stevanin;Y. Trottier;G. Cancel;A. Durr;Gilles David;O. Didierjean;K. Bürk;G. Imbert;F. Saudou;Myriem Abada;I. Gourfinkel‐An;A. Benomar;N. Abbas;T. Klockgether;D. Grid;Y. Agid;J. Mandel;A. Brice
编码多谷氨酰胺的三核苷酸CAG重复序列的扩大与五种神经退行性疾病有关，包括脊髓小脑性共济失调(SCA)1和SCA3或马查多-约瑟夫病(SCA3/MJD)，这是两种I型常染色体显性遗传性小脑性共济失调(ADCA)。使用1C2抗体来识别大的多聚谷氨酰胺束，特别是那些被扩张的抗体，我们最近报道了在另一种形式的ADCA I型SCA2以及表现出不同表型的ADCA II型患者的淋巴母细胞中检测到病理性谷氨酰胺扩张的蛋白质。我们现在已经筛选了一大系列ADCA患者或孤立的小脑性共济失调患者，以确定是否存在多谷氨酰胺扩张的蛋白质。在40个ADCA I型家系中有16个家系检测到150 kDa的sca2蛋白，相当于所有ADCA I型家系的24%，远高于SCA1在本组患者中的发生率(13%)。SCA2蛋白的信号强度与发病时的年龄负相关，正如预期的扩大和不稳定的三核苷酸重复突变所预期的那样。在所有已鉴定的SCA2家系中，该病通过与SCA2基因座紧密连锁的标记进行分离。此外，在9个ADCA II型家系患者的淋巴母细胞中检测到一种与疾病分离的特异性130 kDa蛋白，其中一名患者的大脑皮层中也可见该蛋白，表明其在神经系统中的翻译。最后，在其余ADCA患者或孤立的小脑性共济失调患者的淋巴母细胞中，没有检测到含有扩展的聚谷氨酰胺束的新的疾病相关蛋白。
Expansion of trinucleotide CAG repeats coding for polyglutamine has been implicated in five neurodegenerative disorders, including spinocerebellar ataxia (SCA) 1 and SCA3 or Machado-Joseph disease (SCA3/MJD), two forms of type I autosomal dominant cerebellar ataxias (ADCA). Using the 1C2 antibody which specifically recognizes large polyglutamine tracts, particularly those that are expanded, we recently reported the detection of proteins with pathological glutamine expansions in lymphoblasts from another form of ADCA type I, SCA2, as well as from patients presenting with the distinct phenotype of ADCA type II. We now have screened a large series of patients with ADCA or isolated cases with cerebellar ataxia, for the presence of proteins with polyglutamine expansions. A 150 kDa SCA2 protein was detected in 16 out of 40 families with ADCA type I. This corresponds to 24% of all ADCA type I families, which is much more frequent than SCA1 in this series of patients (13%). The signal intensity of the SCA2 protein was negatively correlated to age at onset, as expected for an expanded and unstable trinucleotide repeat mutation. The disease segregated with markers closely linked to the SCA2 locus in all identified SCA2 families. In addition, a specific 130 kDa protein, which segregated with the disease, was detected in lymphoblasts of patients from nine families with ADCA type II. It was also visualized in the cerebral cortex of one of the patients, demonstrating its translation in the nervous system. Finally, no new disease-related proteins containing expanded polyglutamine tracts could be detected in lymphoblasts from the remaining patients with ADCA or isolated cases with cerebellar ataxia.
抗体研究的证据表明亨廷顿病基因中的 CAG 重复在蛋白质中表达。
影响因子：
3.5
作者：
Jou,YS;Myers,RM
通讯作者：
Myers,RM