Disruption of the Serine/Threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation
Disruption of the Serine/Threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation
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DOI：
10.1086/375538
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发表时间：
2003-06-01
影响因子：
9.8
通讯作者：
Gécz, J
中科院分区：
文献类型：
--
作者：
Kalscheuer, VM;Tao, J;Gécz, J
X-连锁West综合征，也称为“X-连锁婴儿痉挛”（ISSX），以早发性全身性癫痫发作、心律失常和智力迟钝为特征。最近，我们发现大多数婴儿痉挛症的X连锁家族都携带有与Aristaless-related homeobox基因（ARX）相关的突变，该基因定位于Xp21.3-p22.1区间，这些患者的临床表现可以从轻度精神发育迟滞到伴有其他神经系统异常的重度ISSX不等。在这里，我们报告了一项研究，两个严重影响的女性患者显然从头平衡X;常染色体易位，都破坏了丝氨酸-苏氨酸激酶9（STK 9）基因，这地图远端ARX的Xp22.3区域。我们发现STK 9在正常女性体细胞中受到X失活的影响，而在这两名患者中功能缺失，这是因为正常X的优先失活。在两个不相关的患者谁具有相同的表型（包括早发性严重婴儿痉挛，深刻的全球发展停滞，心律失常，严重的精神发育迟滞）相同的基因的中断强烈表明，缺乏功能性STK 9蛋白导致严重ISSX和STK 9是这种疾病的第二个X染色体基因座。
X-linked West syndrome, also called "X-linked infantile spasms" (ISSX), is characterized by early-onset generalized seizures, hvpsarrhythmia, and mental retardation. Recently, we have shown that the majority of the X-linked families with infantile spasms carry mutations in the aristaless-related homeobox gene (ARX), which maps to the Xp21.3-p22.1 interval, and that the clinical picture in these patients can vary from mild mental retardation to severe ISSX with additional neurological abnormalities. Here, we report a study of two severely affected female patients with apparently de novo balanced X;autosome translocations, both disrupting the serine-threonine kinase 9 (STK9) gene, which maps distal to ARX in the Xp22.3 region. We show that STK9 is subject to X-inactivation in normal female somatic cells and is functionally absent in the two patients, because of preferential inactivation of the normal X. Disruption of the same gene in two unrelated patients who have identical phenotypes (consisting of early-onset severe infantile spasms, profound global developmental arrest, hypsarrhythmia, and severe mental retardation) strongly suggests that lack of functional STK9 protein causes severe ISSX and that STK9 is a second X-chromosomal locus for this disorder.