Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, 117198 Moscow, Russia.
Genes (Basel). 2023 Jan 31;14(2):366. doi: 10.3390/genes14020366.
The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749).
The child presented with convulsive syndrome on the third day of life. Generalized convulsive seizures were accompanied by electroencephalographic patterns corresponding to epileptiform activity. Proband WES expanded to trio sequencing was performed.
A differential diagnosis was made between symptomatic (dysmetabolic, structural, infectious) neonatal seizures and benign neonatal seizures. There were no data in favor of the dysmetabolic, structural, or infectious nature of seizures. Molecular karyotyping and whole exome sequencing were not informative. Trio WES revealed a de novo variant in the gene (1:160087612T > C, p.Phe326Ser, NM_004983), for which, according to the OMIM database, no association with the disease has been described to date. Three-dimensional modeling was used to predict the structure of the KCNJ9 protein using the known structure of its homologs. According to the predictions, Phe326Ser change possibly disrupts the hydrophobic contacts with the valine side chain. Destabilization of the neighboring structures may undermine the formation of GIRK2/GIRK3 tetramers necessary for their proper functioning.
We believe that the identified variant may be the cause of the disease in this patient but further studies, including the search for other patients with the variants, are needed.
下一代测序（NGS）成本的降低使得这种方法可以用于单基因疾病（MDs）的新生儿筛查。在本报告中，我们描述了一名参与 EXAMEN 项目（ClinicalTrials.gov 标识符：NCT05325749）的新生儿的临床病例。
患儿在出生后第三天出现惊厥综合征。全身性惊厥发作伴有与癫痫样活动相对应的脑电图模式。对先证者进行了扩展至三人测序的 WES。
在症状性（代谢性、结构性、感染性）新生儿惊厥和良性新生儿惊厥之间做出了鉴别诊断。没有数据支持代谢性、结构性或感染性惊厥的性质。分子核型分析和全外显子组测序没有提供信息。三人 WES 显示 基因（1:160087612T > C，p.Phe326Ser，NM_004983）中有一个新生变异，根据 OMIM 数据库，迄今尚未描述该变异与疾病的关联。使用已知的同源物结构，使用三维建模来预测 KCNJ9 蛋白的结构。根据预测，Phe326Ser 变化可能破坏与缬氨酸侧链的疏水接触。邻近结构的不稳定可能破坏 GIRK2/GIRK3 四聚体的形成，而这些四聚体是其正常功能所必需的。
我们认为，所鉴定的变异可能是该患者疾病的原因，但需要进一步研究，包括寻找其他具有 变异的患者。
