Rapid exome sequencing for children with severe acute encephalopathy – A case series

IF 1.6 4区 医学 Q3 GENETICS & HEREDITY European journal of medical genetics Pub Date : 2024-02-05 DOI:10.1016/j.ejmg.2024.104918
Clair Habib , Tamar Paperna , Rinat Zaid , Sarit Ravid , Josef Ben Ari , Galit Tal , Karin Weiss , Tova Hershkovitz
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Abstract

Increasingly, next-generation sequencing (NGS) is becoming an invaluable tool in the diagnosis of unexplained acute neurological disorders, such as acute encephalopathy/encephalitis. Here, we describe a brief series of pediatric patients who presented at the pediatric intensive care unit with severe acute encephalopathy, initially suspected as infectious or inflammatory but subsequently diagnosed with a monogenic disorder.

Rapid exome sequencing was performed during the initial hospitalization of three unrelated patients, and results were delivered within 7–21 days. All patients were previously healthy, 1.5–3 years old, of Muslim Arab descent, with consanguineous parents. One patient presenting with acute necrotizing encephalopathy (ANEC). Her sister presented with ANEC one year prior.

Exome sequencing was diagnostic in all three patients. All were homozygous for pathogenic and likely-pathogenic variants associated with recessive disorders; MOCS2, NDUFS8 and DBR1. Surprisingly, the initial workup was not suggestive of the final diagnosis.

This case series demonstrates that the use of rapid exome sequencing is shifting the paradigm of diagnostics even in critical care situations and should be considered early on in children with acute encephalopathy. A timely diagnosis can direct initial treatment as well as inform decisions regarding long-term care.

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重症急性脑病患儿的快速外显子组测序--病例系列。
下一代测序(NGS)正日益成为诊断急性脑病/脑炎等原因不明的急性神经系统疾病的宝贵工具。在此,我们简要描述了一系列因严重急性脑病在儿科重症监护室就诊的儿科患者,这些患者最初被怀疑是感染性或炎症性疾病,但随后被诊断为单基因疾病。快速外显子组测序是在三名无关患者最初住院期间进行的,测序结果在 7-21 天内得出。所有患者之前都很健康,1.5-3 岁,阿拉伯穆斯林后裔,父母是近亲。其中一名患者出现急性坏死性脑病(ANEC)。她的姐姐在一年前也出现了急性坏死性脑病。三位患者的外显子组测序结果均为确诊。他们都是与隐性疾病相关的致病变体和可能致病变体的同源基因携带者:MOCS2、NDUFS8 和 DBR1。令人惊讶的是,最初的检查并没有提示最终诊断。该系列病例表明,快速外显子组测序技术的使用正在改变诊断模式,即使在重症监护情况下也是如此。及时的诊断可以指导最初的治疗,并为长期护理的决策提供依据。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
193
审稿时长
66 days
期刊介绍: The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models. Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as : • Dysmorphology and syndrome delineation • Molecular genetics and molecular cytogenetics of inherited disorders • Clinical applications of genomics and nextgen sequencing technologies • Syndromal cancer genetics • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.
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