Department of Pediatrics, Laboratory of Molecular Genetics of Neurodevelopment, University of Padua, Via Giustiniani 3, Padua, Italy.
Clin Genet. 2013 Jul;84(1):82-5. doi: 10.1111/cge.12034. Epub 2012 Nov 7.
Severe early-onset epilepsy is due to a number of known causes, although a clear etiology is not identifiable in up to a third of all the cases. Pathogenic sequence variations in the ARX gene have been described almost exclusively in males, whereas heterozygous female relatives, such as mothers, sisters and even grandmothers have been largely reported as asymptomatic or mildly affected. To investigate the pathogenic role of ARX in refractory epilepsy of early onset even in females, we have screened the ARX sequence in a population of 50 female subjects affected with unexplained epileptic encephalopathy with onset in the first year of life. We report the identification of a novel truncating mutation of the coding region of the ARX gene in a girl with a structurally normal brain. Our findings confirm the role of ARX in the pathogenesis of early epilepsy and underline the importance of screening of the ARX gene in both male and female subjects with otherwise unexplained early onset epileptic encephalopathy.
严重的早发性癫痫是由许多已知原因引起的，尽管多达三分之一的病例无法明确病因。ARX 基因的致病性序列变异几乎仅在男性中被描述，而杂合子女性亲属，如母亲、姐妹，甚至祖母，大多被报道为无症状或轻度受影响。为了研究 ARX 在女性中早发性难治性癫痫中的致病作用，我们在 50 名患有不明原因的癫痫性脑病的女性患者中筛查了 ARX 序列，这些患者的发病年龄均在 1 岁以内。我们报告了一名女孩在 ARX 基因编码区发现了一种新的截断突变，而她的大脑结构正常。我们的发现证实了 ARX 在早期癫痫发病机制中的作用，并强调了在其他方面不明原因的早发性癫痫性脑病的男性和女性患者中筛查 ARX 基因的重要性。
