TY -的T1 Biallelic < em > TSC < / em >基因失活在结节性硬化症复杂JF -神经学乔-神经病学SP - 1716 LP - 1723 - 10.121首页2 / WNL。0 b013e3181e04325六世- 74 - 21 AU - Peter b . Crino AU -爱阿罗尼卡AU -戈登Baltuch盟凯瑟琳·l·内桑森Y1 - 2010/05/25 UR - //www.ez-admanager.com/content/74/21/1716.abstract首页 N2 -背景:一个关键的发展问题是块茎结节性硬化症(TSC)复杂形式通过生殖系和体细胞TSC1或TSC2基因突变。TSC1或TSC2体外和体内的损失导致mTORC1级联激活和核糖体蛋白S6磷酸化(P-S6)。巨细胞(GCs)块茎展览S6磷酸化,表明特异性TSC基因丧失功能。方法:TSC1和TSC2基因突变研究从块茎中提取的DNA部分(n = 6)和microdissected P-S6-labeled GCs通过测序和杂合性丢失(LOH)分析定义生殖系和体细胞突变。结果:1例生殖系TSC1突变的定义和TSC2突变5例中定义。LOH中没有检测到整个块茎部分或microdissected P-S6-labeled gc。TSC1和TSC2测序microdissected P-S6-immunolabeled gc。在5个标本,体细胞突变被发现在单一GCs,没有检测到整个块茎或白细胞DNA片段。四个体细胞突变小说变异(1无稽之谈和3错义突变)和1额外的无稽之谈体细胞突变之前报道作为生殖系突变。 In 1 case, no somatic mutation was identified. There was reduced expression of TSC1 or TSC2 transcripts in the TSC1 or TSC2 associated specimens. In the cases containing a nonsense mutation, no transcript mRNA was detected, suggesting nonsense-mediated degradation. Conclusions: We provide evidence to support the hypothesis that tubers form by biallelic TSC1 or TSC2 gene inactivation reflecting a “2-hit” mechanism of germline and somatic mutational events. AML = angiomyolipoma; DN = dysplastic neuron; FFPE = formalin fixed, paraffin embedded; GC = giant cell; H-E = hematoxylin and eosin; LOH = loss of heterozygosity; TSC = tuberous sclerosis complex. ER -