드라베 증후군의 SCN1A 유전자 변이 양상
SCN1A Variants in Patients with Dravet Syndrome
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목적: 이 연구는 드라베 증후군으로 진단받은 소아 환자들을 대상으로 SCN1A 돌연변이의 특성에 대해 살펴보고자 하였다. 방법: 2007년 1월부터 2015년 5월까지 임상적으로 드라베 증후군으로 확진된 환자 39명을 대상으로 후향적 연구를 진행하였다. SCN1A 변이는 직접 염기 서열 분석법을 이용하여 분석하였고ACMG/AMP 가이드라인에 따라 분류하였다. 결과: 39명의 환자가 포함되었으며 여아는 22명, 남아는 17명이었다. 총 20명(51.2%)의 드라베 증후군 환자에서 SCN1A 병적 돌연변이가 발견되었으며 그 중 15명이 결절 돌연변이, 5명이 과오 돌연변이를가지고 있었다. 나머지 19명의 드라베 증후군 환자들은 10명에서 임상적 의미를 알 수 없는 변이가 관찰되었고 9명에서 양성 소견을 가지고 있었다. 결절 돌연변이는 SCN1A 단백질의 전체 구역에 분포하고있지만, 과오 돌연변이는 pore loop (S5-S6) regions에 좀 더 높은비율로 위치하고 있었다. 결론: 기존의 연구와 달리 본 연구에서는 드라베 증후군 환자의SCN1A 돌연변이의 양성률이 낮게 나왔다. 부모 검사(trio test) 및 추가적인 검사의 중요성이 강조된다.
Abstract
Purpose: The aim of this study is to examine the SCN1A variants in Korean patients with Dravet syndrome. Methods: We conducted a retrospective study of clinically confirmed thirty-nine patients with Dravet syndrome who visit our hospital from January 2007 to May 2015. We analyzed the SCN1A variants by direct sequencing. We analyzed and classified SCN1A variants according to ACMG/AMP (American College of Medical Genetics and Genomics and the Association for Molecular Pathology) guideline. Results: : A total thirty-nine patients (female 22, male 17) were included. Among them, twenty patients (51.2%) with Dravet syndrome had pathogenic or likely pathogenic SCN1A mutations including fifteen truncating mutations (12 nonsense and 3 splice region mutations), 5 missense mutations. The remained variants in nineteen patients with Dravet syndrome classified into ten variants of unknown significances, and 9 benign variants. In our study, truncation mutations are located whole span of SCN1A protein, while half of missense mutations are located at higher density on pore loop (S5-S6) regions. Conclusion: Unlike previous known study, lower positive rate of SCN1A mutation of Dravet syndrome was revealed in our study. The importance of parental test (trio test) and other additional tests have been emphasized.
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