Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy.
Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy.
复制标题
三重全外显子组测序在中国儿童癫痫基因诊断和治疗中的应用
DOI：
10.3389/fnmol.2021.699574
复制
发表时间：
2021
影响因子：
4.8
通讯作者：
Gao F
中科院分区：
文献类型：
--
作者：
Jiang T;Gao J;Jiang L;Xu L;Zhao C;Su X;Shen Y;Gu W;Kong X;Yang Y;Gao F
癫痫是儿科患者中最常见的神经系统疾病之一，伴有其他潜在的神经系统缺陷。确定潜在的病因是至关重要的，以更好地管理的障碍。我们对221例癫痫患儿进行了trio全外显子组测序。先证者分为癫痫发作伴发育迟缓/智力残疾（DD/ID）组和癫痫发作不伴DD/ID组。DD/ID癫痫发作组中71/110（64.5%）例患者和非DD/ID癫痫发作组中21/111（18.9%）例患者发现了致病性（P）或可能致病性（LP）变异（P < 0.001）。共检测到87个不同的P/LP单核苷酸变异（SNV）/插入缺失（Indels），其中55.2%（48/87）是新的。在123个个体（41个家系）中，所有大于100 Kb的非整倍体和P/LP拷贝数变异（CNVs）都可通过全外显子组测序和拷贝数变异测序（CNVseq）来鉴定。通过CNVseq鉴定了9名患者中的10个P/LP CNV和1名患者（患者#56，#47，XXY）中的1个非整倍性变体。在此，我们鉴定了7个基因（NCL、SEPHS 2、PA 2G 4、SLC 35 G2、MYO 1C、GPR 158和POU 3F 1），这些基因具有从头变异，但致病性未知，这些基因以前与癫痫无关。根据分子诊断，32例P/LP变异患者可获得潜在有效的治疗选择。基因检测可能有助于确定早发性癫痫和DD/ID的分子病因，并进一步帮助患者选择适当的治疗策略。
Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands were divided into seizures with developmental delay/intellectual disability (DD/ID) and seizures without DD/ID groups. Pathogenic (P) or likely pathogenic (LP) variants were identified in 71/110 (64.5%) patients in the seizures with DD/ID group and 21/111 (18.9%) patients in the seizures without DD/ID group (P < 0.001). Eighty-seven distinct P/LP single nucleotide variants (SNVs)/insertion deletions (Indels) were detected, with 55.2% (48/87) of them being novel. All aneuploidy and P/LP copy number variants (CNVs) larger than 100 Kb were identifiable by both whole-exome sequencing and copy number variation sequencing (CNVseq) in 123 of individuals (41 pedigrees). Ten of P/LP CNVs in nine patients and one aneuploidy variant in one patient (Patient #56, #47, XXY) were identified by CNVseq. Herein, we identified seven genes (NCL, SEPHS2, PA2G4, SLC35G2, MYO1C, GPR158, and POU3F1) with de novo variants but unknown pathogenicity that were not previously associated with epilepsy. Potential effective treatment options were available for 32 patients with a P/LP variant, based on the molecular diagnosis. Genetic testing may help identify the molecular etiology of early onset epilepsy and DD/ID and further aid to choose the appropriate treatment strategy for patients.
登录
查看更多内容
DOI：
10.1093/bioinformatics/bts526
发表时间：
2012-11-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Plagnol V;Curtis J;Epstein M;Mok KY;Stebbings E;Grigoriadou S;Wood NW;Hambleton S;Burns SO;Thrasher AJ;Kumararatne D;Doffinger R;Nejentsev S
通讯作者：
Nejentsev S
影响因子：
12.3
作者：
Myers CT;Mefford HC
通讯作者：
Mefford HC
影响因子：
5.2
作者：
Redler, Silke;Strom, Tim M.;Wieczorek, Dagmar
通讯作者：
Wieczorek, Dagmar
DOI：
10.1093/bioinformatics/btp698
发表时间：
2010-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li H;Durbin R
通讯作者：
Durbin R
影响因子：
30.8
作者：
Ishida, Saeko;Picard, Fabienne;Rudolf, Gabrielle;Noe, Eric;Achaz, Guillaume;Thomas, Pierre;Genton, Pierre;Mundwiller, Emeline;Wolff, Markus;Marescaux, Christian;Miles, Richard;Baulac, Michel;Hirsch, Edouard;Leguern, Eric;Baulac, Stephanie
通讯作者：
Baulac, Stephanie