Department of Neonatology, Hunan Children's Hospital, Changsha, Hunan, China.
Department of Laboratory Diagnosis, Changsha Kingmed Center for Clinical Laboratory, Changsha, Hunan, China.
Mol Genet Genomic Med. 2024 Jan;12(1):e2354. doi: 10.1002/mgg3.2354.
The genetic background of neonatal encephalopathy (NE) is complicated and early diagnosis is beneficial to optimizing therapeutic strategy for patients.
NE Patients with unclear etiology received regular clinical tests including ammonia test, metabolic screening test, amplitude-integrated electroencephalographic (aEEG) monitoring, brain Magnetic Resonance Imaging (MRI) scanning, and genetic test. The protein structure change was predicted using Dynamut2 and RoseTTAFold.
15 out of a total of 113 NE Patients were detected with newly reported pathogenic variants. In this sub-cohort, (1) seizure was the primary initial symptoms; (2) four patients had abnormal metabolic screening results, and two of them were also diagnosed with excessive blood ammonia concentration; (3) the brain MRI results were irregular in three infants and the brain waves were of moderate-severe abnormality in about a half of the patients. The novel pathogenic variants discovered in this study belonged to 12 genes, and seven of them were predicted to introduce a premature translation termination. In-silicon predictions showed that four variants were destructive to the protein structure of KCNQ2.
Our study expands the mutation spectrum of genes associated with NE and introduces new evidence for molecular diagnosis in this newborn illness.
新生儿脑病（NE）的遗传背景复杂，早期诊断有利于优化患者的治疗策略。
病因不明的 NE 患者接受了常规临床检查，包括氨试验、代谢筛查试验、振幅整合脑电图（aEEG）监测、脑磁共振成像（MRI）扫描和基因检测。使用 Dynamut2 和 RoseTTAFold 预测蛋白质结构变化。
在总共 113 名 NE 患者中，有 15 名患者检测到新报道的致病性变异。在这个亚组中：（1）癫痫是主要的初始症状；（2）有 4 名患者的代谢筛查结果异常，其中 2 名患者还被诊断为血氨浓度过高；（3）3 名婴儿的脑 MRI 结果不规则，约一半患者的脑电波中度至重度异常。本研究发现的新的致病性变异属于 12 个基因，其中 7 个被预测会导致提前终止翻译。硅内预测显示，有 4 个变异会破坏 KCNQ2 蛋白的结构。
本研究扩展了与 NE 相关基因的突变谱，并为这种新生儿疾病的分子诊断提供了新的证据。
