School of Advanced Sciences and Technology, Islamic Azad University-Tehran Medical Sciences, Tehran, Iran.
BMC Pediatr. 2022 Mar 11;22(1):125. doi: 10.1186/s12887-022-03195-4.
Early infantile epileptic encephalopathy is a severe form of epilepsy that is genetically extremely heterogeneous and characterized by seizures or spasms at the beginning of infancy. Homozygous or compound heterozygous mutation in the CAD gene cause early infantile epileptic encephalopathy-50 (EIEE50). This case report describes the clinical and molecular features of three patients affected with early infantile epileptic encephalopathy.
In this report, we describe the clinical features of two deceased daughters and one recently deceased son affected with seizure, muscular hypotonia, and developmental delay. After genetic counseling, blood samples were obtained from the parents, and whole-exome sequencing was performed. Genomic DNA was extracted from whole blood, and mutation analysis was performed using PCR and sequencing methods for the CAD gene. Genetic analysis using the whole-exome sequencing method has detected a novel likely pathogenic mutation on CAD gene, c.2995G > A (p.Val999Met), in heterozygous states in asymptomatic parents and homozygous state in affected newborn son. This mutation has not been reported in the literature for its pathogenicity.
The asymptomatic parents are carriers for the likely pathogenic variant in the CAD gene, and the recently deceased newborn son had the same mutation in a homozygous state. Given that, multiple lines of in silico computational analysis support the detrimental impact of the variant on the gene, and this variant is absent in population databases. Pathogenic mutations in the CAD gene are related to autosomal recessive EIEE50 with similar signs and symptoms to our patients. Ultimately, it is confirmed that this mutation is causative in our patients.
早发性婴儿癫痫性脑病是一种严重的癫痫形式，其遗传极为异质，以婴儿期开始的癫痫发作或痉挛为特征。CAD 基因的纯合子或复合杂合突变导致早发性婴儿癫痫性脑病-50（EIEE50）。本病例报告描述了 3 名受早发性婴儿癫痫性脑病影响的患者的临床和分子特征。
在本报告中，我们描述了 2 名已故女儿和 1 名最近去世的儿子的临床特征，他们患有癫痫、肌肉张力减退和发育迟缓。在遗传咨询后，从父母那里采集了血样，并进行了全外显子组测序。从全血中提取基因组 DNA，使用 PCR 和测序方法对 CAD 基因进行突变分析。使用全外显子组测序方法的遗传分析检测到 CAD 基因中的一种新的可能致病性突变，c.2995G>A（p.Val999Met），在无症状父母中为杂合状态，在受影响的新生儿儿子中为纯合状态。该突变在文献中尚未报道其致病性。
无症状父母是 CAD 基因中可能致病变异的携带者，最近去世的新生儿儿子为纯合状态。鉴于此，多种基于计算机的线分析支持该变异对基因的有害影响，并且该变异不存在于人群数据库中。CAD 基因突变与常染色体隐性 EIEE50 相关，具有与我们患者相似的体征和症状。最终，证实该突变是我们患者的致病原因。
