Abstract：
The MYT1L gene plays a critical role in brain development, promoting the differentiation and proliferation of cells, important for the formation of brain connections. MYT1L is also involved in regulating the development of the hypothalamus, which is a crucial actor in weight regulation. Genetic variants in the MYT1L are associated with a range of developmental disorders, including intellectual disability, autism spectrum disorder, facial dysmorphisms, and epilepsy. The specific role of MYT1L in epilepsy remains elusive and no patients with developmental and epileptic encephalopathy (DEE) have been described so far. In this study, we report a patient with DEE presenting with severe refractory epilepsy, obesity, and behavioral abnormalities. Exome sequencing led to the identification of the heterozygous variant NM_001303052.2: c.1717G>A, p.(Gly573Arg) (chr2-1910340-C-T; GRCh38.p14) in the MYT1L gene. This variant was found to be inherited by the father, who was a mosaic and did not suffer from any neuropsychiatric disorders. Our observations expand the molecular and phenotype spectrum of MYT1L-related disorders, suggesting that affected individuals may present with severe epileptic phenotype leading to neurocognitive deterioration. Furthermore, we show that mosaic parents may not display the disease phenotype, with relevant implications for genetic counseling.
摘要：
MYT1L基因在大脑发育中起着至关重要的作用。促进细胞的分化和增殖，对大脑连接的形成很重要。MYT1L还参与调节下丘脑的发育，这是体重调节的关键角色。MYT1L中的遗传变异与一系列发育障碍有关，包括智力残疾，自闭症谱系障碍，面部畸形，和癫痫。MYT1L在癫痫中的具体作用仍然难以捉摸，到目前为止，尚未描述患有发育性和癫痫性脑病（DEE）的患者。在这项研究中,我们报告了一名DEE患者，表现为严重难治性癫痫，肥胖，和行为异常。外显子组测序导致杂合变体NM_001303052.2的鉴定：c.1717G>A，p.（Gly573Arg）（chr2-1910340-C-T；GRCh38。p14)在MYT1L基因中。这个变体被发现是由父亲继承的，他是马赛克，没有任何神经精神疾病。我们的观察扩展了MYT1L相关疾病的分子和表型谱，提示受影响的个体可能存在严重的癫痫表型，导致神经认知恶化。此外，我们表明马赛克父母可能不显示疾病表型，对遗传咨询有相关意义。
