Naseer Muhammad I, Rasool Mahmood, Abdulkareem Angham A, Bassiouni Randa I, Algahtani Hussein, Chaudhary Adeel G, Al-Qahtani Mohammad H
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. E-mail:
Neurosciences (Riyadh). 2018 Oct;23(4):347-350. doi: 10.17712/nsj.2018.4.20180095.
To identify genetic variation involved in primary microcephaly.
In present study we identified 4 generation Saudi family showing primary microcephaly. We performed whole exome sequencing along with Sanger sequencing to find the genetic defect in this family. This study was conducted in King Abdulaziz University started from 2016 and the results presented in this manuscript are from one of the family.
Two novel missense variants (c.982G>A and c.1273T>A) were identified in heterozygous state in exon 8 of MCPH1 gene. The detected missense variants cause a tyrosine to asparagine substitution of residue 425 and a valine to isoleucine substitution at residue 310. MCPH1 gene encodes a DNA damage response protein. The encoded protein play a role in G2/M DNA damage checkpoint arrest via maintenance of inhibitory phosphorylation of cyclin-dependent kinase 1. The respective mutation was ruled out in 100 control samples.
We found novel compound heterozygous mutation in Saudi family that will help to build database for genetic mutations in population and pave way to devise strategies to tackle such disorders in future.
鉴定与原发性小头畸形相关的基因变异。
在本研究中，我们鉴定了一个显示原发性小头畸形的沙特四代家系。我们进行了全外显子组测序以及桑格测序，以寻找该家系中的基因缺陷。本研究于2016年在阿卜杜勒阿齐兹国王大学开展，本论文所呈现的结果来自其中一个家系。
在MCPH1基因第8外显子中鉴定出两个杂合状态的新错义变异（c.982G>A和c.1273T>A）。检测到的错义变异导致第425位残基的酪氨酸被天冬酰胺取代，以及第310位残基的缬氨酸被异亮氨酸取代。MCPH1基因编码一种DNA损伤反应蛋白。该编码蛋白通过维持细胞周期蛋白依赖性激酶1的抑制性磷酸化，在G2/M期DNA损伤检查点停滞中发挥作用。在100个对照样本中排除了相应的突变。
我们在沙特家系中发现了新的复合杂合突变，这将有助于建立人群基因突变数据库，并为今后制定应对此类疾病的策略铺平道路。
