Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Arch Iran Med. 2023 Apr 1;26(4):186-197. doi: 10.34172/aim.2023.29.
Intellectual disability (ID) is a genetically heterogeneous condition, and so far, 1679 human genes have been identified for this phenotype. Countries with a high rate of parental consanguinity, such as Iran, provide an excellent opportunity to identify the remaining novel ID genes, especially those with an autosomal recessive (AR) mode of inheritance. This study aimed to investigate the most prevalent ID genes identified via next-generation sequencing (NGS) in a large ID cohort at the Genetics Research Center (GRC) of the University of Social Welfare and Rehabilitation Sciences.
First, we surveyed the epidemiological data of 619 of 1295 families in our ID cohort, who referred to the Genetics Research Center from all over the country between 2004 and 2021 for genetic investigation via the NGS pipeline. We then compared our data with those of several prominent studies conducted in consanguineous countries. Data analysis, including cohort data extraction, categorization, and comparison, was performed using the R program version 4.1.2.
We categorized the most common ID genes that were mutated in more than two families into 17 categories. The most common syndromic ID in our cohort was AP4 deficiency syndrome, and the most common non-syndromic autosomal recessive intellectual disability (ARID) gene was . We identified two unrelated families for the 36 ID genes. We found 14 genes in common between our cohort and the Arab and Pakistani groups, of which three genes (, , and ) were repeated more than once.
To date, there has been no comprehensive targeted NGS platform for the detection of ID genes in our country. Due to the large sample size of our study, our data may provide the initial step toward designing an indigenously targeted NGS platform for the diagnosis of ID, especially common ARID in our population.
智力障碍（ID）是一种遗传异质性疾病，迄今为止，已经有 1679 个人类基因被确定与该表型相关。在像伊朗这样父母近亲结婚率较高的国家，有一个很好的机会可以鉴定出其余的新的 ID 基因，特别是那些具有常染色体隐性（AR）遗传模式的基因。本研究旨在调查大学社会福利与康复科学遗传研究中心（GRC）的一个大型 ID 队列通过下一代测序（NGS）确定的最常见的 ID 基因。
首先，我们调查了我们的 ID 队列中 619 个家庭中的 619 个家庭的流行病学数据，这些家庭在 2004 年至 2021 年间通过 NGS 管道从全国各地到遗传研究中心进行遗传调查。然后，我们将我们的数据与在近亲结婚国家进行的几项知名研究的数据进行了比较。数据分析包括使用 R 程序版本 4.1.2 提取、分类和比较队列数据。
我们将在两个以上家庭中发生突变的最常见的 ID 基因分类为 17 个类别。我们队列中最常见的综合征性 ID 是 AP4 缺乏综合征，最常见的非综合征性常染色体隐性智力障碍（ARID）基因是 。我们鉴定了两个无关家庭的 36 个 ID 基因。我们在我们的队列和阿拉伯及巴基斯坦人群中发现了 14 个共同的基因，其中三个基因（、和）不止一次重复出现。
迄今为止，在我们国家还没有针对 ID 基因检测的全面靶向 NGS 平台。由于我们的研究样本量很大，我们的数据可能为设计一个针对我们人群中常见 ARID 的本土靶向 NGS 平台提供了初步步骤。
