Clinical and genetic analysis of PACS2 gene variant in two child patients with developmental and epileptic encephalopathy 66.
10.3760/cma.j.cn511374-20210301-00172
- VernacularTitle:两例发育性癫痫性脑病66型患儿的临床表型及
PACS2基因变异分析
- Author:
Yajun SHEN
1
,
2
;
Yang LI
;
Jia ZHANG
;
Meng YUAN
;
Jinxiu ZHANG
;
Rong LUO
;
Jing GAN
Author Information
1. 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)
2. Key Laboratory of Development and Maternal and Child Diseases of Sichuan Province, Chengdu, Sichuan 610041, China. gordonrachel@163.com.
- Publication Type:Journal Article
- MeSH:
Child;
Epilepsy, Generalized;
Family;
Genetic Testing;
Humans;
Magnetic Resonance Imaging;
Vesicular Transport Proteins/genetics*;
Whole Exome Sequencing
- From:
Chinese Journal of Medical Genetics
2021;38(10):969-972
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the clinical phenotype and genetic characteristics of two children with developmental epileptic encephalopathy type 66.
METHODS: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.
RESULTS: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.
CONCLUSION: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.
