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首页> 外文期刊>BMC Medical Genomics >Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate
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Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate

机译：大多数近亲阿拉伯神经病患者的外显子组测序可提供较高的潜在分子诊断率

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Background Neurodevelopment is orchestrated by a wide range of genes, and the genetic causes of neurodevelopmental disorders are thus heterogeneous. We applied whole exome sequencing (WES) for molecular diagnosis and in silico analysis to identify novel disease gene candidates in a cohort from Saudi Arabia with primarily Mendelian neurologic diseases. Methods We performed WES in 31 mostly consanguineous Arab families and analyzed both single nucleotide and copy number variants (CNVs) from WES data. Interaction/expression network and pathway analyses, as well as paralog studies were utilized to investigate potential pathogenicity and disease association of novel candidate genes. Additional cases for candidate genes were identified through the clinical WES database at Baylor Miraca Genetics Laboratories and GeneMatcher. Results We found known pathogenic or novel variants in known disease genes with phenotypic expansion in 6 families, disease-associated CNVs in 2 families, and 12 novel disease gene candidates in 11 families, including KIF5B , GRM7 , FOXP4 , MLLT1 , and KDM2B . Overall, a potential molecular diagnosis was provided by variants in known disease genes in 17 families (54.8?%) and by novel candidate disease genes in an additional 11 families, making the potential molecular diagnostic rate ~90?%. Conclusions Molecular diagnostic rate from WES is improved by exome-predicted CNVs. Novel candidate disease gene discovery is facilitated by paralog studies and through the use of informatics tools and available databases to identify additional evidence for pathogenicity. Trial registration Not applicable.
机译：背景技术神经发育由广泛的基因协调，因此神经发育障碍的遗传原因是异质的。我们应用全外显子组测序（WES）进行分子诊断和计算机分析，以鉴定来自沙特阿拉伯主要患有孟德尔神经系统疾病的队列中的新型疾病基因候选者。方法我们在31个主要近亲的阿拉伯家庭中进行了WES，并从WES数据中分析了单核苷酸和拷贝数变异（CNV）。相互作用/表达网络和途径分析，以及旁系同源研究被用来调查新候选基因的潜在致病性和疾病关联。通过Baylor Miraca Genetics Laboratories和GeneMatcher的临床WES数据库确定了候选基因的其他病例。结果我们在6个家族的表型扩展中发现了已知疾病基因的已知致病或新变体，在2个家族中发现了与疾病相关的CNV，在11个家族中发现了12个新的疾病基因候选者，包括KIF5B，GRM7，FOXP4，MLLT1和KDM2B。总体而言，潜在的分子诊断是通过17个家族中已知疾病基因的变异（54.8％）和另外11个家族中的新候选疾病基因提供的，使得潜在的分子诊断率约为90％。结论外显子组预测的CNV可提高WES的分子诊断率。旁系同源物研究以及通过使用信息学工具和可用数据库来鉴定致病性的其他证据，促进了新的候选疾病基因的发现。试用注册不适用。

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