Department of Neurology, Pediatrics, and Biomedical Genetics, Center for Neural Development & Disease, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA.
Neurogenetics. 2013 May;14(2):99-111. doi: 10.1007/s10048-013-0356-y. Epub 2013 Feb 7.
MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. We report 16 new patients with MEF2C haploinsufficiency, including the oldest reported patient with MEF2C deletion at 5q14.3. We detail the neurobehavioral phenotype, epilepsy, and abnormal movements, and compare our subjects with those previously reported in the literature. We also investigate Mef2c expression in the developing mouse forebrain. A spectrum of neurofunctional deficits emerges, with hyperkinesis a consistent finding. Epilepsy varied from absent to severe, and included intractable myoclonic seizures and infantile spasms. Subjects with partial MEF2C deletion were statistically less likely to have epilepsy. Finally, we confirm that Mef2c is present both in dorsal primary neuroblasts and ventral gamma-aminobutyric acid(GABA)ergic interneurons in the forebrain of the developing mouse. Given interactions with several key neurodevelopmental genes such as ARX, FMR1, MECP2, and TBR1, it appears that MEF2C plays a role in several developmental stages of both dorsal and ventral neuronal cell types.
MEF2C 杂合不足综合征是一种新兴的神经发育障碍，与智力障碍、自闭症特征、癫痫和异常运动有关。我们报告了 16 名新的 MEF2C 杂合不足患者，包括报告的最年长的 5q14.3 MEF2C 缺失患者。我们详细描述了神经行为表型、癫痫和异常运动，并将我们的研究对象与文献中以前报道的进行了比较。我们还研究了发育中的小鼠前脑的 Mef2c 表达。出现了一系列神经功能缺陷，其中多动是一致的发现。癫痫从无到严重不等，包括难治性肌阵挛性癫痫发作和婴儿痉挛。MEF2C 部分缺失的患者发生癫痫的可能性统计学上较低。最后，我们证实 Mef2c 存在于发育中老鼠前脑的背侧原神经细胞和腹侧γ-氨基丁酸(GABA)能中间神经元中。由于与 ARX、FMR1、MECP2 和 TBR1 等几个关键神经发育基因的相互作用，MEF2C 似乎在背侧和腹侧神经元细胞类型的几个发育阶段都发挥作用。
