| 1 | Psychiatr. Genet. 2008 Dec 18: 295-301 |
|---|---|
| PMID | 19018235 |
| 标题 | 神经发育精神疾病中同源基因基因基因基因基因组的编码三核苷酸重复的多态性。 |
| 抽象的 | Autism (MIM#209850) andschizophrenia(MIM#181500) are both neurodevelopmental psychiatric disorders characterized by a highly genetic component. Homeogenes and forkhead genes encode transcription factors, which have been involved in brain development and cell differentiation. Thus, they are relevant candidate genes for psychiatric disorders. Genetic studies have reported an association between autism and DLX2, HOXA1, EN2,ARX, and FOXP2 genes whereas only three studies of EN2, OTX2, and FOXP2 were performed onschizophrenia。Interestingly, most of these candidate genes contain trinucleotide repeats coding for polyamino acid stretch in which instability can be the cause of neurodevelopmental disorders. Our goal was to identify variations of coding trinucleotide repeats inschizophrenia，自闭症和特发性智力低下。 We screened the coding trinucleotide repeats of OTX1, EN1, DLX2, HOXA1, and FOXP2 genes in populations suffering fromschizophrenia(247 patients), autism (98 patients), and idiopathic mental retardation (56 patients), and compared them with control populations (112 super controls and 202 healthy controls). 在DLX2，HOXA1和FOXP2基因中发现了编码三核苷酸重复序列的新颖缺失和插入。在对照组中检测到这些变化中的大多数，并且在患者和对照组之间没有观察到它们的分布差异。但是，FOXP2中的两种不同多态性仅在自闭症患者中发现，并且必须将重复变化的功能后果表征为与特定的临床特征。 这项研究并未鉴定出在神经发育精神疾病中OTX1，EN1，DLX2，HOXA1和FOXP2候选基因中三核苷酸重复序列的特定疾病风险变异。 |
| SCZ关键字 | schizophrenia |
| 2 | Epilepsia 2011 May 52: 984-92 |
| PMID | 21426321 |
| 标题 | A novel mutation in the aristaless domain of the ARX gene leads to Ohtahara syndrome, global developmental delay, and ambiguous genitalia in males and neuropsychiatric disorders in females. |
| 抽象的 | ARX，与歧义相关的同源基因基因与脑，睾丸和胰腺发育有关。ARXmutations are associated with various forms of epilepsy, developmental delay, and ambiguous genitalia in humans. A mouse model that recapitulates X-linked lissencephaly with ambiguous genitalia (XLAG) is far from elucidating the substrate for phenotypes that differentARX突变原因。此外，尽管表型多态性与X连锁显性相关ARXmutations, heterozygous female carriers have not been thoroughly studied. Reviewing records of patients withARX突变，婴儿癫痫和心理运动迟缓，我们分析了一个有小说的家庭ARX男性和女性（包括Ohtahara综合征）中具有不同表型的突变。 儿童医院的波士顿患者记录对接受婴儿癫痫性脑病的患者进行了回顾性筛查ARXsequencing based on clinical suspicion. Identified families were analyzed for genetic and neuropsychiatric phenomena. 该概率是男性患有Ohtahara综合征，模棱两可的生殖器，精神运动延迟和中枢神经系统失效，原因是ARXmutation in exon 5, causing a frameshift in the aristaless domain. Heterozygous females demonstrated neurocognitive/psychiatric phenomena including learning difficulties, anxiety, depression, andschizophrenia。 这是第一个报道Ohtaharasyndrome with abnormal genital and psychomotor development in the setting of this novelARX外显子5中的突变。基于概率的独特表型和具有神经认知/精神病性疾病的杂合女性的存在，本研究描述ARXmutations in epilepsy and neuropsychiatric disease, underscoring the importance ofARX在神经元的发育中，脑电活动，认知和行为。 |
| SCZ关键字 | schizophrenia |
| 3 | Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2014 Sep 369: -1 |
| PMID | 25135975 |
| 标题 | Regulation of histone H3K4 methylation in brain development and disease. |
| 抽象的 | The growing list of mutations implicated in monogenic disorders of the developing brain includes at least seven genes (ARX，Cul4b，KDM5A，KDM5C，KMT2A，KMT2C，KMT2D），具有功能丧失突变，影响组蛋白H3赖氨酸4甲基化的适当调控，一种染色质标记，在全基因组范围内与活性基因表达广泛相关，并与其具有活性基因表达相关单，二甲基和三甲基化形式在启动子和增强子以及其他调节序列中差异富集。除了这些罕见的遗传综合征外，H3K4甲基化失调还可能在某些被诊断为自闭症或自闭症的病例的病理生理学中起作用schizophrenia, two conditions which on a genome-wide scale are associated with H3K4 methylation changes at hundreds of loci in a subject-specific manner. Importantly, the reported alterations for some of the diseased brain specimens included a widespread broadening of H3K4 methylation profiles at gene promoters, a process that could be regulated by the UpSET(KMT2E/MLL5)-histone deacetylase complex. Furthermore, preclinical studies identified maternal immune activation, parental care and monoaminergic drugs as environmental determinants for brain-specific H3K4 methylation. These novel insights into the epigenetic risk architectures of neurodevelopmental disease will be highly relevant for efforts aimed at improved prevention and treatment of autism and psychosis spectrum disorders. |
| SCZ关键字 | schizophrenia |
| 4 | 精神分裂。res。2016年3月-1：-1 |
| PMID | 26972474 |
| 标题 | 精神分裂症前额叶皮质中类蛋白酶和生长抑素神经元的发育调节剂的表达改变。 |
| 抽象的 | 前额叶皮层（PFC）抑制性神经元的功能障碍，该神经元表达钙结合蛋白白蛋白或神经肽生长抑素在schizophreniamay be related to disturbances in the migration, phenotypic specification, and/or maturation of these neurons. These pre- and postnatal developmental stages are regulated in a cell type-specific manner by various transcription factors and co-activators, fibroblast growth factor receptors (FgfR), and other molecular markers. Consequently, we used quantitative PCR to quantify mRNA levels for these developmental regulators in the PFC of 62schizophreniasubjects in whom parvalbumin and somatostatin neuron disturbances were previously reported, and in antipsychotic-exposed monkeys. Relative to unaffected comparison subjects, subjects withschizophreniaexhibited elevated mRNA levels for 1) the transcription factor MafB, which is expressed by parvalbumin and somatostatin neurons as they migrate from the medial ganglionic eminence to the cortex, 2) the transcriptional coactivator PGC-1?, which is expressed postnatally by parvalbumin neurons to maintain parvalbumin levels and inhibitory function, and 3) FgfR1, which is required for the migration and phenotypic specification of parvalbumin and somatostatin neurons. Elevations in these markers were most prominent in youngerschizophreniasubjects and were not present in antipsychotic-exposed monkeys. Finally, expression levels of other important developmental regulators (i.e. Dlx1, Dlx5, Dlx6, SATB1, Sip1/Zeb2, ST8SIA4, cMaf, Nkx6.2, andARX) were not altered inschizophrenia。分子标记子集的过表达在白蛋白和生长抑素神经元的产后和产后发育中具有明显作用，这可能反映出在面对其他侮辱时维持这些神经元发展的补偿机制。 |
| SCZ关键字 | schizophrenia |