Department of Child and Adolescent Neuropsychiatry, Spedali Civili, Brescia, Italy.
Am J Med Genet A. 2010 Dec;152A(12):3133-7. doi: 10.1002/ajmg.a.33701.
Recently, it has been reported that longer expansions of the polyalanine tract of the ARX gene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARX gene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARX is involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations.
最近有报道称，ARX 基因多聚丙氨酸区的扩展更长可能导致抑制爆发模式的早发性婴儿脑病，并且该重复区域的长度可能与电临床图片的严重程度有关。我们描述了两名男性个体的病史，他们均来自同卵双胞胎姐妹，患有大田原综合征（OS），随后发展为 West 综合征表型和癫痫性脑病。在这两个孩子中，我们发现了一个以前未报道的 ARX 基因突变（c.1604T>A），导致氨基酸序列中的亮氨酸被谷氨酰胺取代。两位母亲和外祖母携带相同的突变，该突变在家族中与疾病表型分离。本研究证实 ARX 参与了隐源性早发性癫痫性脑病（如 OS）的发病机制，并表明电临床图片的严重程度可能不仅与多聚丙氨酸区扩展的程度相关，而且与不同致病突变的功能效应相关。
