基于全外显子组测序的复杂儿童癫痫综合征诊断——临床应用的队列研究

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Alfiya Fasaludeen, Manna Jose, U Aswathi, Moinak Banerjee, Soumya Sundaram, Ashalatha Radhakrishnan, Madhusoodanan Urulangodi, Dinesh Gupta, Sheela Nampoothiri, Ramshekhar N Menon
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引用次数: 0

摘要

来自次大陆的关于全外显子组测序(WES)在儿童期发病的耐药癫痫(DRE)综合征,特别是发育性和癫痫性脑病(DEE)的电临床表型中的应用的研究在文献中很少见。DRE表型推定为遗传病因的患者中,发病年龄为3岁的占23.4%,发育迟缓的占80.6%。WES中致病/可能致病变异的总产率为38.9%(68/175,其中19个为新发变异);三组为41.1%。68例中有45例(66.2%)主要是新生变异,最常见的致病变异是错义变异(74%)。与局灶性癫痫相比,发病年龄较小、女性和Dravet综合征的电临床诊断与较高的发生率相关。25/68(36.8%)的病例认为精准医疗是可行的。我们的研究揭示了在儿童发病的DRE/DEE的新生变异中,三wes的显著产量。女性、发病年龄早和特定的电临床表型更有可能确定单基因病因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Whole Exome Sequencing Based Diagnostics in Complex Childhood Epilepsy Syndromes-A Cohort Study on Clinical Utility.

Studies from the subcontinent on the utility of Whole Exome Sequencing (WES) in electro-clinical phenotypes of childhood-onset drug-resistant epilepsy (DRE) syndromes, particularly the developmental and epileptic encephalopathies (DEE), are rare in the literature. Patients with DRE phenotypes of presumed genetic etiology with an age of onset of epilepsy < 12 years, with/without developmental encephalopathy, were included in this study. Our study cohort (N = 175) included 158 trios, 6 duos, and 11 proband-only samples. Age at onset of seizures was ≤ 3 years in 76.6% and > 3 years in 23.4%, with developmental delay noted in 80.6% of the cohort. The overall yield of pathogenic/likely pathogenic variants in WES was 38.9% (68/175, 19 were novel); for trio-WES it was 41.1%. Predominantly de novo variants accounted for 45 out of 68 cases (66.2%), and the most frequent disease-causing variants were missense (74%). Younger age at onset of epilepsy, female gender and electroclinical diagnosis of Dravet syndrome were associated with a higher yield as opposed to focal epilepsies. Precision medicine was considered tenable in 25/68 (36.8%) cases. Our study reveals a significant yield of trio-WES for de novo variants in childhood-onset DRE/DEE. Female gender, early age at onset, and specific electro-clinical phenotypes have a higher likelihood of identifying a monogenic etiology.

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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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