Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements.
Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements.
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FRRS1L中Boricua Founder变异导致癫痫性脑病伴多动运动
DOI：
10.1177/0883073820953001
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发表时间：
2021-03
影响因子：
1.9
通讯作者：
Schneider MC
中科院分区：
文献类型：
--
作者：
Abdelmoumen I;Jimenez S;Valencia I;Melvin J;Legido A;Diaz-Diaz MM;Griffith C;Massingham LJ;Yelton M;Rodríguez-Hernández J;Schnur RE;Walsh LE;Cristancho AG;Bergqvist CA;McWalter K;Mathieson I;Belbin GM;Kenny EE;Ortiz-Gonzalez XR;Schneider MC
描述15名波多黎各（Boricua）血统的早期婴儿癫痫性脑病（EIEE-37）伴显著运动障碍的儿童中纯合子FRRS 1 L c.737_739delGAG（p.Gly246del）变体的创始突变效应和临床表型。EIEE-37是由FRRS 1 L基因中功能变体的双等位基因缺失引起的，FRRS 1 L基因对AMPA受体功能至关重要，导致顽固性癫痫和运动障碍。一项回顾性、多中心病历审查，对临床基因检测发现的具有相同纯合子FRRS 1 L（p.Gly246del）致病性变异的患者进行了审查。收集关于神经发育结局、神经影像学、电图特征和抗癫痫药物临床反应的临床信息。15例患者来自12个不同的家庭的波多黎各血统是纯合子的FRRS 1 L（p.Gly246del）致病性变异，年龄范围从1至25岁。癫痫发作时间为6 ~ 24个月。所有人都有张力减退，严重的整体发育迟缓，大多数有多动不自主运动。在生命的第一年发育退化是常见的（86%）。脑电图显示66%（10/15）的高度心律失常，许多年龄较大的儿童演变为Lennox-Gastaut综合征。6例患者在脑磁共振成像（MRI）上显示进行性容量丢失和/或小脑萎缩。我们描述了迄今为止最大的癫痫性脑病患者队列。我们估计，0.76%的波多黎各血统的未受影响的个人携带这种致病性变异由于创始人效应。FRRS 1 L（p.Gly246del）Boricua变异体纯合子儿童表现出早期发育退化和癫痫的非常同质的表型，从婴儿痉挛开始，演变为Lennox-Gastaut综合征伴多动性运动障碍。
To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.
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影响因子：
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