Diagnostic Utility of Exome Data Reanalysis After In Silico Multi-Gene Panels or Clinical Exome Testing for Patients With Epilepsy and Developmental Delay/Intellectual Disability: A Retrospective Cohort Study.

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Alexanne Cuillerier, Andrea Goodman, Chloe Lawrence, Noémie Villeneuve-Cloutier, Christine M Armour, Priya T Bhola, Danielle K Bourque, Melissa T Carter, Joanna Lazier, Sarah L Sawyer, Maha Saleh, Chitra Prasad, Victoria M Siu, Kym M Boycott, Taila Hartley, David A Dyment, Tugce B Balci
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引用次数: 0

Abstract

Epilepsy is a relatively common condition with genetic factors contributing significantly to its etiology. Advances in next-generation sequencing have dramatically increased the number of known epilepsy genes, improving diagnostic capabilities and patient care. However, 50%-80% of epilepsy patients remain undiagnosed after genomic testing, which includes chromosomal microarray, multigene panels, and genome-wide sequencing. Reanalysis of existing exome sequencing data has shown promise in increasing diagnostic yield. In this study, we reanalyzed exome sequencing data from 87 individuals with unsolved epilepsy and developmental delay or intellectual disability in Ontario, Canada. Our approach combined clinical and translational research methodologies to identify genetic variants linked to epilepsy. We obtained a diagnostic yield of 14.9%, solving 13 participants, with 11 involving known genes and two novel gene discoveries. In addition, 11 potential diagnoses were identified, suggesting that further investigation could confirm additional diagnoses. Factors such as the inclusion of additional family data, new disease-gene associations, and technological advancements contributed to these findings. This study highlights the importance of reanalysis as a cost-effective and timely approach to improving diagnostic yield in epilepsy associated with neurodevelopmental delay.

多基因芯片或临床外显子组检测后外显子组数据再分析对癫痫和发育迟缓/智力残疾患者的诊断价值:一项回顾性队列研究
癫痫是一种相对常见的疾病,遗传因素对其病因有重要影响。新一代测序技术的进步极大地增加了已知癫痫基因的数量,提高了诊断能力和患者护理。然而,50%-80%的癫痫患者在基因组检测后仍未得到诊断,其中包括染色体微阵列、多基因面板和全基因组测序。对现有外显子组测序数据的重新分析显示出提高诊断率的希望。在这项研究中,我们重新分析了加拿大安大略省87名未解决的癫痫和发育迟缓或智力残疾患者的外显子组测序数据。我们的方法结合临床和转化研究方法来确定与癫痫相关的遗传变异。我们获得了14.9%的诊断率,解决了13个参与者,其中11个涉及已知基因和两个新发现的基因。此外,还发现了11个潜在的诊断,表明进一步的调查可以确认更多的诊断。诸如纳入额外的家庭数据、新的疾病基因关联和技术进步等因素促成了这些发现。这项研究强调了再分析作为一种成本效益高且及时的方法对提高神经发育迟缓相关癫痫的诊断率的重要性。
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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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