West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation
West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation
复制标题
DOI：
10.1136/jmedgenet-2013-101752
复制
发表时间：
2013-11-01
影响因子：
4
通讯作者：
Edvardson, Simon
中科院分区：
文献类型：
--
作者：
Banne, Ehud;Atawneh, Osama;Edvardson, Simon
West综合征（WS）是一种儿童期癫痫性脑病，其特征为通常发生在1岁以下的聚集性痉挛，EEG上的高度心律失常，这是众所周知的难以定义，发育停滞或退化。WS的发病率为1：3200活产，预后取决于病因。高达80%的有症状的WS儿童患有精神发育迟滞，约50%发展为Lennox-Gastaut综合征。使用纯合性定位，然后进行外显子组测序，我们确定了一个ADP核糖基化因子（ARF）鸟嘌呤核苷酸交换因子2（布雷菲德菌素A抑制）（ARFGEF 2）突变在5个相关的婴儿与WS。ARFGEF 2参与激活ARF通过加速取代结合鸟苷二磷酸（GDP）与鸟苷三磷酸（GTP），并参与高尔基体转运。ARFGEF 2的突变以前只描述过一次，导致小头畸形和脑室周围异位。在这里，我们描述了一种新的ARFGEF 2突变在5个相关的患者表现为WS，小头畸形，脑室周围异位和薄胼胝体。
West syndrome (WS) is an epileptic encephalopathy of childhood, defined by the presence of clustered spasms usually occurring before the age of 1year, hypsarrhythmia on EEG that is notoriously difficult to define, and developmental arrest or regression. The incidence of WS is 1:3200 live births with an aetiology-dependent prognosis. Up to 80% of children with symptomatic WS suffer from mental retardation, and approximately 50% develop Lennox-Gastaut syndrome. Using homozygosity mapping followed by exome sequencing, we identified a ADP-ribosylation factor (ARF) guanine nucleotide-exchange factor two (brefeldin A-inhibited) (ARFGEF2) mutation in five related infants with WS. ARFGEF2 is involved in the activation of ARFs by accelerating replacement of bound guanosine diphosphate (GDP) with Guanosine triphosphate (GTP), and is involved in Golgi transport. A mutation in ARFGEF2 has been previously described only once, causing microcephaly and periventricular heterotopia. Here, we describe a novel ARFGEF2 mutation in five related patients presenting with WS, microcephaly, periventricular heterotopia and thin corpus callosum.