Harripaul Ricardo, Noor Abdul, Ayub Muhammad, Vincent John B
Molecular Neuropsychiatry & Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada.
Institute of Medical Science, University of Toronto, Toronto, Ontario M5T 1R8, Canada.
Cold Spring Harb Perspect Med. 2017 Mar 1;7(3):a026864. doi: 10.1101/cshperspect.a026864.
Genetic or genomic mutation is a major cause of intellectual disability (ID). However, despite the generally anticipated strong genotype/phenotype correlation for ID, there are huge obstacles to gene identification, except perhaps where very distinct syndromic features are observed, because of the high degree of genetic heterogeneity and wide variability of phenotype for different mutations or even with the same mutation within a single gene. A recent review estimates in excess of 2500 genes for ID. Fortunately for researchers and diagnosticians alike, the recent advent of massively parallel sequencing technologies, or next-generation sequencing (NGS) has made an apparently impossible task tractable. Here, we review the ongoing research endeavors to identify new disease genes, as well as strategies and approaches at the clinical level.
遗传或基因组突变是智力残疾（ID）的主要原因。然而，尽管通常预计ID会有很强的基因型/表型相关性，但由于高度的遗传异质性以及不同突变甚至同一基因内相同突变的表型广泛变异性，除了可能观察到非常明显的综合征特征的情况外，基因鉴定存在巨大障碍。最近的一项综述估计，与ID相关的基因超过2500个。幸运的是，对于研究人员和诊断医生来说，大规模平行测序技术即新一代测序（NGS）的出现使得一项看似不可能的任务变得易于处理。在这里，我们综述了正在进行的旨在鉴定新疾病基因的研究工作，以及临床层面上所采用的策略和方法。
