Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada.
Genes (Basel). 2022 Apr 19;13(5):715. doi: 10.3390/genes13050715.
Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy associated with mutations in the , and genes. A previous study linking ADLTE with two mutations that resulted in the substitution of a highly conserved glycine residue for serine (G150S) or a frameshift mutation that swapped the last three C-terminal amino acids for 59 extra residues (A1065fs) concluded that the mutations increased enzymatic activity and promoted cell contraction. The roles of the Molecule Interacting with CasL 1 (MICAL1) protein in tightly regulated semaphorin signaling pathways suggest that activating MICAL1 mutations could result in defects in axonal guidance during neuronal development. Further studies would help to illuminate the causal relationships of these point mutations with ADLTE. In this review, we discuss the proposed pathogenesis caused by mutations in these three genes, with a particular emphasis on the G150S point mutation discovered in . We also consider whether these types of activating mutations could be linked to cancer.
常染色体显性颞叶癫痫（ADLTE）是一种与 、 和 基因突变相关的遗传性局灶性癫痫。先前的研究将 ADLTE 与两种突变联系起来，这两种突变导致高度保守的甘氨酸残基被丝氨酸取代（G150S）或移码突变，导致最后三个 C 末端氨基酸被 59 个额外的残基取代（A1065fs），结论是突变增加了酶活性并促进了细胞收缩。分子间相互作用与 CasL 1（MICAL1）蛋白在严格调控的 semaphorin 信号通路中的作用表明，激活 MICAL1 突变可能导致神经元发育过程中轴突导向缺陷。进一步的研究将有助于阐明这些点突变与 ADLTE 的因果关系。在这篇综述中，我们讨论了这三个基因的突变所引起的发病机制，特别强调了在 中发现的 G150S 点突变。我们还考虑了这些类型的激活突变是否与癌症有关。
