Ithal Dhruva, Sukumaran Salil K, Bhattacharjee Debanjan, Vemula Alekhya, Nadella Ravi, Mahadevan Jayant, Sud Reeteka, Viswanath Biju, Purushottam Meera, Jain Sanjeev
Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India.
Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India.
Asian J Psychiatr. 2021 May;59:102640. doi: 10.1016/j.ajp.2021.102640. Epub 2021 Apr 2.
Severe mental illnesses such as schizophrenia and bipolar disorder have complex inheritance patterns, involving both common and rare variants. Whole exome sequencing is a promising approach to find out the rare genetic variants. We had previously reported several rare variants in multiplex families with severe mental illnesses. The current article tries to summarise the biological processes and pattern of expression of genes harbouring the aforementioned variants, linking them to known clinical manifestations through a methodical narrative review. Of the 28 genes considered for this review from 7 families with multiple affected individuals, 6 genes are implicated in various neuropsychiatric manifestations including some variations in the brain morphology assessed by magnetic resonance imaging. Another 15 genes, though associated with neuropsychiatric manifestations, did not have established brain morphological changes whereas the remaining 7 genes did not have any previously recorded neuropsychiatric manifestations at all. Wnt/b-catenin signaling pathway was associated with 6 of these genes and PI3K/AKT, calcium signaling, ERK, RhoA and notch signaling pathways had at least 2 gene associations. We present a comprehensive review of biological and clinical knowledge about the genes previously reported in multiplex families with severe mental illness. A 'disease in dish approach' can be helpful to further explore the fundamental mechanisms.
精神分裂症和双相情感障碍等严重精神疾病具有复杂的遗传模式，涉及常见和罕见变异。全外显子组测序是一种很有前景的发现罕见遗传变异的方法。我们之前曾报道过重度精神疾病的多重家庭中的几种罕见变异。本文试图通过系统的叙述性综述总结携带上述变异的基因的生物学过程和表达模式，并将它们与已知的临床表现联系起来。在本次综述所考虑的来自7个有多个患病个体的家庭的28个基因中，有6个基因与各种神经精神表现有关，包括通过磁共振成像评估的一些脑形态学变化。另外15个基因虽然与神经精神表现有关，但尚未确定有脑形态学改变，而其余7个基因则根本没有任何先前记录的神经精神表现。Wnt/β-连环蛋白信号通路与其中6个基因相关，PI3K/AKT、钙信号、ERK、RhoA和Notch信号通路至少有2个基因关联。我们对先前在重度精神疾病多重家庭中报道的基因的生物学和临床知识进行了全面综述。“培养皿中的疾病方法”可能有助于进一步探索其基本机制。
