조기영아성간질성뇌병증 환자에서 de novo로 확인된 HCN1 유전자 돌연변이 1예 보고
De novo HCN1 Mutation Identified by Next-Generation Sequencing in a Patient with Early Infantile Epileptic Encephalopathy: Case Report
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초록
조기영아성간질성뇌병증은 이른 나이에 반복적 발작 증상을 보이는 일련의 뇌질환을 총칭한다. 이 질환은 다양한 유전자에 의해 발병하는 것으로 알려져 있으며, HCN1 유전자도 그 중 하나이다. 본 증례에서 저자들은 조기영아성간질성뇌병증 환아에서 HCN1 유전자의 새로운 de novo 변이가 발견된 사례를 보고하고자 한다. 특별한 출생력이나 가족력이 없는 환아가 생후 4개월 때부터 간질지속증이 발생하여 내원하였다. 차세대염기서열분석에 의해 HCN1 유전자의 c.794T>A(p.Leu265His) 변이가 이형접합형으로 검출되었다. 해당 변이는 정상인 데이터베이스에서 관찰되지 않고, in silico 병인 분석상 병적일 가능성이 높다고 예측되었다. 추가로 실시한 부모의 Sanger sequencing 결과 상기 변이는 de novo 변이임이 확인되었다. 본 변이의 확인을 통해 환자의 예후를 예측해 볼 수 있었고 표적치료의 가능성을 확인하였다.
Abstract
Early infantile epileptic encephalopathy (EIEE) is a group of brain disorders characterized by spontaneous seizures occurring at an early age. EIEE is caused by mutations in various genes, including HCN1. Here, we report a Korean patient with EIEE carrying a de novo mutation in the HCN1 gene. A female infant with unremarkable birth and family history showed status epilepticus four months after birth. Next-generation sequencing analysis revealed a heterozygous missense mutation, c.794T>A(p.Leu265His), in HCN1. The variant was not observed in any population control dataset, and in silico pathogenicity analyses predicted the variant to be pathogenic. Subsequent family testing by Sanger sequencing confirmed that the variant was a de novo mutation. These findings provide insights for predicting patient prognosis and the possibility of developing targeted therapy.
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