Abstract：
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 KCNJ9 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 KCNJ9 variants, are needed.
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 KCNJ9 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 KCNJ9 variants, are needed.
摘要：
背景：下一代测序（NGS）成本的降低允许将这种方法用于新生儿筛查单基因疾病（MD）。在这份报告中,我们描述了一个新生儿参与EXAMEN项目的临床病例(ClinicalTrials.govIdentifier:NCT05325749).
方法：患儿在出生后第三天出现抽搐综合征。广泛性惊厥性癫痫发作伴随着与癫痫样活动相对应的脑电图模式。进行扩展至三重测序的ProbandWES。
结果：在症状（代谢异常，结构,感染性）新生儿癫痫发作和良性新生儿癫痫发作。没有支持代谢异常的数据，结构,或癫痫发作的传染性。分子核型分析和全外显子组测序没有提供信息。TrioWES揭示了KCNJ9基因中的从头变异(1:160087612T>C,p.Phe326Ser,NM_004983),为此，根据OMIM数据库，迄今为止，尚未描述与该疾病的关联。使用三维建模来预测KCNJ9蛋白的结构,使用其同源物的已知结构。根据预测,Phe326Ser变化可能破坏与缬氨酸侧链的疏水接触。相邻结构的失稳可能会破坏其正常功能所必需的GIRK2/GIRK3四聚体的形成。
结论：我们认为所鉴定的变异可能是该患者疾病的原因，但进一步的研究，包括寻找其他患有KCNJ9变种的患者，是需要的。
方法：患儿在出生后第三天出现抽搐综合征。
结果：在症状（代谢异常，
结论：我们认为所鉴定的变异可能是该患者疾病的原因，但进一步的研究，
