Naseer Muhammad Imran, Rasool Mahmood, Abdulkareem Angham Abdulrahman, Chaudhary Adeel G, Zaidi Syed Kashif, Al-Qahtani Mohammad H
Muhammad Imran Naseer, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
Mahmood Rasool, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
Pak J Med Sci. 2019;35(3):764-770. doi: 10.12669/pjms.35.3.36.
Primary microcephaly (MCPH) is a rare autosomal recessive disorder characterized by impaired congenital reduction of brain size along with head circumference and intellectual disability. MCPH is a heterogeneous disorder and more than twenty four genes associated with this disease have been identified so far. The objective of this study was to find out the novel genes or mutations leading to the genetic defect in a Saudi family with primary microcephaly.
Whole exome sequencing was carried out to find the novel mutation and the results was further validated using Sanger sequencing analysis. This study was done in the Center of excellence in Genomic Medicine and Research, King Abdulaziz University under KACST project during 2017 and 2018.
We report a novel compound heterozygous mutations c.797C>T in exon 7 and c.1102G>A in exon 9 of the WD repeat domain 62 (WDR62) (OMIM 604317) gene in two affected siblings in Saudi family with intellectual disability, speech impediments walking difficulty along with primary microcephaly. Two rare, missense variants were detected in heterozygous state in the gene in these two affected individuals from the heterozygous parents.
A compound heterozygous mutations c.797C>T in exon 7 and c.1102G> A in exon 9 of the gene was identified. gene is very important gene and mutation can lead to neuro developmental defects, brain malformations, reduced brain and head size. These results should be taken into consideration during prognostic discussions and mutation spectrum with affected patients and their families in the Saudi population.
原发性小头畸形（MCPH）是一种罕见的常染色体隐性疾病，其特征为先天性脑尺寸、头围减小以及智力残疾。MCPH是一种异质性疾病，迄今为止已鉴定出24多个与该疾病相关的基因。本研究的目的是在一个患有原发性小头畸形的沙特家庭中找出导致遗传缺陷的新基因或突变。
进行全外显子组测序以寻找新的突变，并使用桑格测序分析进一步验证结果。本研究于2017年至2018年在阿卜杜勒阿齐兹国王大学基因组医学与研究卓越中心，在沙特科技城项目下开展。
我们报告了沙特家庭中两名受影响的兄弟姐妹中WD重复结构域62（WDR62）（OMIM 604317）基因第7外显子的新复合杂合突变c.797C>T和第9外显子的c.1102G>A，他们有智力残疾、言语障碍、行走困难以及原发性小头畸形。在来自杂合子父母的这两名受影响个体中，该基因以杂合状态检测到两个罕见的错义变体。
鉴定出了该基因第7外显子的复合杂合突变c.797C>T和第9外显子的c.1102G>A。该基因是非常重要的基因，突变可导致神经发育缺陷、脑畸形、脑和头尺寸减小。在与沙特人群中受影响患者及其家庭进行预后讨论和突变谱分析时，应考虑这些结果。
