Verrotti Alberto, Palka Chiara, Prezioso Giovanni, Alfonsi Melissa, Calabrese Giuseppe, Palka Giandomenico, Chiarelli Francesco
Department of Pediatrics, University of Perugia, Perugia, Italy.
Cytogenet Genome Res. 2015;146(2):115-119. doi: 10.1159/000438502. Epub 2015 Aug 13.
We report the first case of an 18p11.32 deletion, detected by array CGH, associated with a drug-resistant form of atypical absence epilepsy, global developmental delay and no signs of holoprosencephaly (HPE). In particular, this region encompasses 19 genes, and none of these genes have been strictly associated with epilepsy. Among these, TGIF1 is expressed in the fetal and adult nervous system, and its deletion has been related to central nervous system diseases. TGIF1 deletions have previously been reported in patients with a comparable phenotype as seen in our case and in children whose neurological signs and symptoms were considerable, but not epileptiform. Mutations and deletions involving the TGIF1 gene have been described in patients with HPE in an autosomal dominant model of inheritance. However, TGIF1 mutations have also been reported in normal individuals and in patients with mental retardation or showing a very mild phenotype, suggesting the characteristic of incomplete penetrance and variable expressivity. Therefore, a TGIF1 deletion may not be always related to HPE, and it may have a link to the development of epilepsy.
我们报告了首例通过阵列比较基因组杂交（array CGH）检测到的18p11.32缺失病例，该病例与耐药型非典型失神癫痫、全面发育迟缓相关，且无脑前脑无裂畸形（HPE）迹象。具体而言，该区域包含19个基因，且这些基因均未与癫痫严格相关。其中，TGIF1在胎儿及成人神经系统中表达，其缺失与中枢神经系统疾病有关。此前在具有与我们病例类似表型的患者以及神经体征和症状明显但无癫痫样表现的儿童中曾报道过TGIF1缺失。在常染色体显性遗传模式下，HPE患者中曾描述过涉及TGIF1基因的突变和缺失。然而，正常个体以及智力发育迟缓或表现出非常轻微表型的患者中也报道过TGIF1突变，提示其具有不完全外显率和可变表达性的特征。因此，TGIF1缺失可能并非总是与HPE相关，且可能与癫痫的发生有关。
