SOBP Is Mutated in Syndromic and Nonsyndromic Intellectual Disability and Is Highly Expressed in the Brain Limbic System
SOBP Is Mutated in Syndromic and Nonsyndromic Intellectual Disability and Is Highly Expressed in the Brain Limbic System
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DOI：
10.1016/j.ajhg.2010.10.005
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发表时间：
2010-11-12
影响因子：
9.8
通讯作者：
Basel-Vanagaite, Lina
中科院分区：
文献类型：
--
作者：
Birk, Efrat;Har-Zahav, Adi;Basel-Vanagaite, Lina
智力障碍 (ID) 影响普通人群的 1%-3% 我们最近报道了一个患有常染色体隐性智力低下伴上颌前突和斜视 (MRAMS) 综合征的家庭 所报道的一名 ID 患者没有畸形特征，但确实患有颞叶癫痫和精神病 我们报道了 SOBP 中截短突变的鉴定，该突变负责在同一家庭中引起综合征性和非综合征性 ID 编码的蛋白质SOBP 眼正弦结合蛋白直系同源物，是一种核锌指蛋白 在小鼠中 Sobp（也称为 Jxc1）对于 Corti 器官的模式形成至关重要，我们的一名患者患有亚临床耳蜗听力损失，但没有明显的耳蜗异常 出生后小鼠大脑的原位 RNA 表达研究显示，在活跃突触发生的时间间隔，边缘系统中存在强烈表达 边缘系统调节学习、记忆和情感行为，但边缘系统ID 中突变的其他基因的电路表达是不寻常的 通过使用蛋白质组学比较 +/Jc 与 Jc/Jc 小鼠大脑的蛋白质含量，我们检测到 24 种蛋白质的表达差异大于 1 5 倍，其中包括两种相互作用的蛋白质，dynamin 和 pacsin1 这项研究表明，突变的 SOBP 参与了人类综合征性和非综合征性 ID 的精神病
Intellectual disability (ID) affects 1%-3% of the general population We recently reported on a family with autosomal recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis We report on the identification of a truncating mutation in the SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family The protein encoded by the SOBP sine oculis binding protein ortholog, is a nuclear zinc finger protein In mice Sobp (also known as Jxc1) is critical for patterning of the organ of Corti, one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual By comparing the protein content of the +/Jc to Jc/Jc mice brains with the use of proteomics we detected 24 proteins with greater than 1 5 fold differences in expression including two interacting proteins, dynamin and pacsin1 This study shows mutated SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans