从遗传角度来说,亨廷顿病属于常染色体显性遗传方式,由于患者检出43次的CAG重复,>40次,属于全突变范围,即完全外显,所有携带者均会发病。患者检出HTT基因杂合型突变,该基因异常遗传给子女的风险均为50%,同样,患者兄弟姐妹等其他一级亲属携带风险也为50%。这种情况下,患者血缘亲属的遗传咨询则尤为必要,也同样建议进行该...
导读 亨廷顿病是由亨廷顿蛋白基因(HTT)外显子的CAG重复扩增引起的,该外显子被翻译成亨廷顿蛋白(HTT)中的聚谷氨酰胺延伸。作者先前的研究表明,携带一个扩增的CAG重复序列的HTT mRNA被不完全剪接而产生HTT1a,这是一个仅有外显子1的转录本,...
4. Walker FO. Huntington’s disease. Lancet 2007; 369(9557): 218-28. 5. Mangiarini L,Sathasivam K,Seller M,et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice [J]. Cell,1996,87(3):493 -506. 6. ...
今天我们要讲的主角是亨廷顿病致病基因HTT。HTT基因研究概况 该基因与亨廷顿病（Huntington disease,HD）直接相关，致病区域在其1号外显子上。在正常人中，HTT基因的1号外显子数量只有不超过35个连续的CAG重复，编码一段Huntingtin蛋白上的多聚谷氨酸。当这种CAG重复超过35个时，HD发病概率随着重复的增加而上升。目前H...
5. Mangiarini L,Sathasivam K,Seller M,et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice [J]. Cell,1996,87(3):493 -506. 6. Ravikumar B,Vacher C,Berger Z,et al. Inhibition of mTOR in-duces autopha...
5. Mangiarini L,Sathasivam K,Seller M,et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice [J]. Cell,1996,87(3):493 -506. 6. Ravikumar...
在内源性HTT启动子和调节元件的控制下,转基因BAC226Q小鼠体内表达了含有226个CAG-CAA重复序列的全长人HTT。为了确定全长人HTT序列在转基因FVB小鼠基因组中的拷贝数和插入位点,研究采用了全基因组测序,结果显示在FVB小鼠基因组的8号染色体Chr8:46084002处插入了两个人类HTT拷贝。与11月龄的另一种亨廷顿模型BACHD...
HTTgenehuntingtinpermutationHuntington disease (Huntington chorea, HD) is a severe neurodegenerative disease determined by polyglutamine. Polyglutamine expansion in exon 1 of the HTT gene causes Huntington disease. To date, less than 35 CAG triplets are suggested to be present in normal alleles. ...
Trinucleotide (CAG) repeat expansions longer than 39 in the huntingtin (HTT) gene cause Huntington’s disease (HD). The frequency of intermediate alleles (IA) with a length of 27–35 in the general population is not fully known, but studied in specific m
在正常人中,HTT基因的1号外显子数量只有不超过35个连续的CAG重复,编码一段Huntingtin蛋白上的多聚谷氨酸。当这种CAG重复超过35个时,HD发病概率随着重复的增加而上升。目前HD在欧美高加索白人中的发病率在0.005%~0.01%之间,属于罕见病范畴,但由于该病致病基因单一,发现时间早,而且症状涉及运动,认知,精神等多重障碍,...