PDF(Pubmed)
Abstract：
UNASSIGNED: This study aimed to summarize the clinical phenotype and genotype of children with epilepsy caused by GABRA1 gene variants.
UNASSIGNED: Eight epilepsy patients, who were admitted to Qilu Hospital of Shandong University from 2015 to 2021, were enrolled in the study. GABRA1 gene variants were detected by whole-exome sequencing. Epilepsy clinical manifestations, electroencephalography, neuroimaging characteristics and treatment methods were retrospectively analyzed.
UNASSIGNED: Among the eight patients, four were males and four were females. Epilepsy onset age was between 3 and 8 months of age. Two patients had a family history of epilepsy. Six cases were de novo variants, and two were hereditary variants. Two children carried the same pathogenic variants, and five carried novel pathogenic variants that had not been reported internationally. The types of seizures were diverse, including focal seizures in five cases, generalized tonic-clonic seizures in five cases, and spasms in two cases. Electroencephalography of seven cases showed abnormal background rhythms, and six cases showed abnormal discharge during the interictal period. No obvious abnormalities were found on magnetic resonance imaging in five cases. All eight children had different degrees of developmental retardation.
UNASSIGNED: De novo pathogenic variants in GABRA1 are more common than inherited pathogenic variants, and most epilepsy symptoms begin in the first year of life, manifesting with a variety of seizure types and developmental delays. Conventional treatment usually involves one or more drugs; although drug treatment can control seizures in some cases, cognitive and developmental deficits often exist. The five newly discovered pathogenic variants enrich the GABRA1 gene pathogenic variant spectrum.
UNASSIGNED: Eight epilepsy patients, who were admitted to Qilu Hospital of Shandong University from 2015 to 2021, were enrolled in the study. GABRA1 gene variants were detected by whole-exome sequencing. Epilepsy clinical manifestations, electroencephalography, neuroimaging characteristics and treatment methods were retrospectively analyzed.
UNASSIGNED: Among the eight patients, four were males and four were females. Epilepsy onset age was between 3 and 8 months of age. Two patients had a family history of epilepsy. Six cases were de novo variants, and two were hereditary variants. Two children carried the same pathogenic variants, and five carried novel pathogenic variants that had not been reported internationally. The types of seizures were diverse, including focal seizures in five cases, generalized tonic-clonic seizures in five cases, and spasms in two cases. Electroencephalography of seven cases showed abnormal background rhythms, and six cases showed abnormal discharge during the interictal period. No obvious abnormalities were found on magnetic resonance imaging in five cases. All eight children had different degrees of developmental retardation.
UNASSIGNED: De novo pathogenic variants in GABRA1 are more common than inherited pathogenic variants, and most epilepsy symptoms begin in the first year of life, manifesting with a variety of seizure types and developmental delays. Conventional treatment usually involves one or more drugs; although drug treatment can control seizures in some cases, cognitive and developmental deficits often exist. The five newly discovered pathogenic variants enrich the GABRA1 gene pathogenic variant spectrum.
摘要：
■本研究旨在总结由GABRA1基因变异引起的癫痫患儿的临床表型和基因型。
■八位癫痫患者，2015年至2021年山东大学齐鲁医院收治的患者被纳入研究。通过全外显子组测序检测GABRA1基因变体。癫痫临床表现,脑电图,回顾性分析神经影像学特征及治疗方法。
■在8名患者中，四个是男性，四个是女性。癫痫发病年龄在3至8个月之间。2例患者有癫痫家族史。6例为从头变异，两个是遗传变体。两个孩子携带相同的致病变异，5种携带了尚未在国际上报道的新型致病变异。癫痫发作的类型多种多样，包括五例局灶性癫痫发作，五例全身性强直-阵挛性癫痫发作，和痉挛两种情况。7例脑电图显示背景节律异常，6例患者在治疗期间出现异常出院。5例磁共振成像未见明显异常。8例患儿均有不同程度的发育迟缓。
■GABRA1中的从头致病变异比遗传致病变异更常见，大多数癫痫症状始于生命的第一年，表现为各种癫痫发作类型和发育迟缓。常规治疗通常涉及一种或多种药物；尽管药物治疗在某些情况下可以控制癫痫发作，认知和发育缺陷经常存在。五个新发现的致病变异丰富了GABRA1基因致病变异谱。
■八位癫痫患者，2015年至2021年山东大学齐鲁医院收治的患者被纳入研究。通过全外显子组测序检测GABRA1基因变体。癫痫临床表现,脑电图,回顾性分析神经影像学特征及治疗方法。
■在8名患者中，四个是男性，四个是女性。癫痫发病年龄在3至8个月之间。2例患者有癫痫家族史。6例为从头变异，两个是遗传变体。两个孩子携带相同的致病变异，5种携带了尚未在国际上报道的新型致病变异。癫痫发作的类型多种多样，包括五例局灶性癫痫发作，五例全身性强直-阵挛性癫痫发作，和痉挛两种情况。7例脑电图显示背景节律异常，6例患者在治疗期间出现异常出院。5例磁共振成像未见明显异常。8例患儿均有不同程度的发育迟缓。
■GABRA1中的从头致病变异比遗传致病变异更常见，大多数癫痫症状始于生命的第一年，表现为各种癫痫发作类型和发育迟缓。常规治疗通常涉及一种或多种药物；尽管药物治疗在某些情况下可以控制癫痫发作，认知和发育缺陷经常存在。五个新发现的致病变异丰富了GABRA1基因致病变异谱。
