PDF(Pubmed)
Abstract：
UNASSIGNED: This study presents the clinical phenotypes and genetic analysis of seven patients with benign familial infantile epilepsy (BFIE) diagnosed by whole-exome sequencing.
UNASSIGNED: The clinical data of seven children with BFIE diagnosed at the Department of Neurology, Children\'s Hospital Affiliated to Zhengzhou University between December 2017 and April 2022 were retrospectively analyzed. Whole-exome sequencing was used to identify the genetic causes, and the variants were verified by Sanger sequencing in other family members.
UNASSIGNED: The seven patients with BFIE included two males and five females ranging in age between 3 and 7 months old. The main clinical phenotype of the seven affected children was the presence of focal or generalized tonic-clonic seizures, which was well controlled by anti-seizure medication. Cases 1 and 5 exhibited predominantly generalized tonic-clonic seizures accompanied by focal seizures while cases 2, 3, and 7 displayed generalized tonic-clonic seizures, and cases 4 and 6 had focal seizures. The grandmother and father of cases 2, 6, and 7 had histories of seizures. However, there was no family history of seizures in the remaining cases. Case 1 carried a de novo frameshift variant c.397delG (p.E133Nfs*43) in the proline-rich transmembrane protein 2 (PRRT2) gene while case 2 had a nonsense variant c.46G > T (p.Glu16*) inherited from the father, and cases 3-7 carried a heterozygous frameshift variant c.649dup (p.R217Pfs*8) in the same gene. In cases 3 and 4, the frameshift variant was de novo, while in cases 5-7, the variant was paternally inherited. The c.397delG (p.E133Nfs*43) variant is previously unreported.
UNASSIGNED: This study demonstrated the effectiveness of whole-exome sequencing in the diagnosis of BFIE. Moreover, our findings revealed a novel pathogenic variant c.397delG (p.E133Nfs*43) in the PRRT2 gene that causes BFIE, expanding the mutation spectrum of PRRT2.
UNASSIGNED: The clinical data of seven children with BFIE diagnosed at the Department of Neurology, Children\'s Hospital Affiliated to Zhengzhou University between December 2017 and April 2022 were retrospectively analyzed. Whole-exome sequencing was used to identify the genetic causes, and the variants were verified by Sanger sequencing in other family members.
UNASSIGNED: The seven patients with BFIE included two males and five females ranging in age between 3 and 7 months old. The main clinical phenotype of the seven affected children was the presence of focal or generalized tonic-clonic seizures, which was well controlled by anti-seizure medication. Cases 1 and 5 exhibited predominantly generalized tonic-clonic seizures accompanied by focal seizures while cases 2, 3, and 7 displayed generalized tonic-clonic seizures, and cases 4 and 6 had focal seizures. The grandmother and father of cases 2, 6, and 7 had histories of seizures. However, there was no family history of seizures in the remaining cases. Case 1 carried a de novo frameshift variant c.397delG (p.E133Nfs*43) in the proline-rich transmembrane protein 2 (PRRT2) gene while case 2 had a nonsense variant c.46G > T (p.Glu16*) inherited from the father, and cases 3-7 carried a heterozygous frameshift variant c.649dup (p.R217Pfs*8) in the same gene. In cases 3 and 4, the frameshift variant was de novo, while in cases 5-7, the variant was paternally inherited. The c.397delG (p.E133Nfs*43) variant is previously unreported.
UNASSIGNED: This study demonstrated the effectiveness of whole-exome sequencing in the diagnosis of BFIE. Moreover, our findings revealed a novel pathogenic variant c.397delG (p.E133Nfs*43) in the PRRT2 gene that causes BFIE, expanding the mutation spectrum of PRRT2.
摘要：
■这项研究提供了通过全外显子组测序诊断的7例良性家族性婴儿癫痫（BFIE）患者的临床表型和遗传分析。
■7名在神经内科确诊的BFIE患儿的临床资料,对2017年12月至2022年4月郑州大学附属儿童医院进行回顾性分析。全外显子组测序用于确定遗传原因，并通过Sanger测序在其他家族成员中验证了变异。
■7名BFIE患者包括2名男性和5名女性，年龄在3至7个月之间。7名受影响儿童的主要临床表型是存在局灶性或全身性强直阵挛性癫痫发作，通过抗癫痫药物很好地控制了。病例1和5主要表现为全身性强直-阵挛性癫痫发作并伴有局灶性癫痫发作，而病例2、3和7表现为全身性强直-阵挛性癫痫发作。病例4和6有局灶性癫痫发作。病例2、6和7的祖母和父亲有癫痫发作史。然而,其余病例没有癫痫发作的家族史.案例1携带从头移码变体c.397delG（p。富含脯氨酸的跨膜蛋白2（PRRT2）基因中的E133Nfs*43），而病例2具有无义变体c.46G>T（p。Glu16*)继承自父亲，病例3-7携带杂合移码变体c.649dup（p。R217Pfs*8)在同一基因中。在病例3和4中，移码变体是从头的，而在病例5-7中，变异体是父系遗传的。c.397delG（p。E133Nfs*43）变体以前未报道。
■本研究证明了全外显子组测序在BFIE诊断中的有效性。此外，我们的发现揭示了一种新的致病变异c.397delG（p.E133Nfs*43）在引起BFIE的PRRT2基因中，扩展PRRT2的突变谱。
■7名在神经内科确诊的BFIE患儿的临床资料,对2017年12月至2022年4月郑州大学附属儿童医院进行回顾性分析。全外显子组测序用于确定遗传原因，并通过Sanger测序在其他家族成员中验证了变异。
■7名BFIE患者包括2名男性和5名女性，年龄在3至7个月之间。7名受影响儿童的主要临床表型是存在局灶性或全身性强直阵挛性癫痫发作，通过抗癫痫药物很好地控制了。病例1和5主要表现为全身性强直-阵挛性癫痫发作并伴有局灶性癫痫发作，而病例2、3和7表现为全身性强直-阵挛性癫痫发作。病例4和6有局灶性癫痫发作。病例2、6和7的祖母和父亲有癫痫发作史。然而,其余病例没有癫痫发作的家族史.案例1携带从头移码变体c.397delG（p。富含脯氨酸的跨膜蛋白2（PRRT2）基因中的E133Nfs*43），而病例2具有无义变体c.46G>T（p。Glu16*)继承自父亲，病例3-7携带杂合移码变体c.649dup（p。R217Pfs*8)在同一基因中。在病例3和4中，移码变体是从头的，而在病例5-7中，变异体是父系遗传的。c.397delG（p。E133Nfs*43）变体以前未报道。
■本研究证明了全外显子组测序在BFIE诊断中的有效性。此外，我们的发现揭示了一种新的致病变异c.397delG（p.E133Nfs*43）在引起BFIE的PRRT2基因中，扩展PRRT2的突变谱。
