Shen Yajun, Li Yang, Zhang Jia, Yuan Meng, Zhang Jinxiu, Luo Rong, Gan Jing
Department of Pediatrics, West China Second University Hospital, Sichuan University/Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education (Sichuan University); Key Laboratory of Development and Maternal and Child Diseases of Sichuan Province, Chengdu, Sichuan 610041, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Oct 10;38(10):969-972. doi: 10.3760/cma.j.cn511374-20210301-00172.
To explore the clinical phenotype and genetic characteristics of two children with developmental epileptic encephalopathy type 66.
Genomic DNA was extracted from peripheral blood samples of the two children and their parents. Whole exome sequencing (WES) was carried out and suspected variant was verified by Sanger sequencing.
The main manifestations of the two children were neonatal onset seizures, hypotonia, global developmental delay, and facial dysmorphisms. Cranial MRI showed delayed myelination in case 1 and cerebellar dysgenesis in case 2. WES has identified a de novo pathogenic variant in the PACS2 gene in both patients, namely c.625G>A (p.Glu209Lys)(NM_001100913.3), which was reported as a pathogenic variant before. This variant was predicted to be pathogenic according to the American College of Medical Genetics and Genomics guideline (PS2+PM2+PP3). The seizures were controlled after combination treatment of sodium valproate and levetiracetam in both cases. At last follow-up, the motor and intellectual development of the 2 cases were improved. Compared with the cases reported, the clinical symptoms and signs of our cases were relatively mild, and the treatment effects were fairly good.
The variant of c.625G>A (p.Glu209Lys) in PACS2 gene is a hotspot variant of developmental epileptic encephalopathy 66. Gene testing can facilitate the clinical diagnosis and treatment.
探讨2例66型发育性癫痫性脑病患儿的临床表型及遗传学特征。
提取2例患儿及其父母外周血样本中的基因组DNA。进行全外显子组测序（WES），并通过Sanger测序验证可疑变异。
2例患儿主要表现为新生儿期起病的癫痫发作、肌张力低下、全面发育迟缓及面部畸形。头颅磁共振成像（MRI）显示，病例1为髓鞘发育延迟，病例2为小脑发育不全。WES在2例患者中均鉴定出PACS2基因的一个新生致病性变异，即c.625G>A（p.Glu209Lys）（NM_001100913.3），该变异此前已被报道为致病性变异。根据美国医学遗传学与基因组学学会指南（PS2+PM2+PP3），该变异被预测为致病性变异。2例患者经丙戊酸钠和左乙拉西坦联合治疗后癫痫发作得到控制。末次随访时，2例患者的运动和智力发育均有所改善。与已报道病例相比，我们病例的临床症状和体征相对较轻，治疗效果较好。
PACS2基因c.625G>A（p.Glu209Lys）变异是66型发育性癫痫性脑病的热点变异。基因检测有助于临床诊断和治疗。
