Rasool Iqra Ghulam, Zahoor Muhammad Yasir, Ahmed Irfan, Iqbal Muhammad, Shafqat Shehla, Anjum Aftab Ahmad, Shehzad Wasim
Molecular Biology and Biotechnology Section, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
Department of Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
Genes Genomics. 2023 Apr;45(4):457-465. doi: 10.1007/s13258-022-01219-y. Epub 2022 Feb 12.
Intellectual disability (ID) is a neurodevelopmental condition, affecting 1-3% of the population. Genetic factors play a key role causing the limitation in intellectual functioning and adaptive behavior. The heterogeneity of ID makes it more difficult for genetic and clinical diagnosis. Mapping of variants through next generation DNA sequencing in consanguineous families would help to understand the molecular parthenogenesis of ID.
The aim of this study was to describe the genetic variants of ID in consanguineous Pakistani families.
We analyzed four unrelated consanguineous Pakistani families having an intellectual disability through whole exome sequencing (WES). Data was analyzed using different bioinformatics tools and software.
We mapped four novel variants in different ID genes. Each variant is found in different family, co-segregating with a recessive pattern of inheritance. The variants found are; c.1437delG:p.Asn480Thrfs*10, mapped in FKRP, c.2041 C>A:p.Leu681Met in HIRA, c.382 C>T:p.Arg128Cys in BDH1 and c.267+1G>A:p.? identified in TRAPPC6B.
These variants help in demonstration of status and molecular basis of intellectual disability in Pakistani population leading to provision of genetic counseling services and a contribution in disease variant database.
智力残疾（ID）是一种神经发育疾病，影响着1%至3%的人口。遗传因素在导致智力功能和适应性行为受限方面起着关键作用。ID的异质性使得遗传和临床诊断更加困难。通过对近亲家庭进行下一代DNA测序来绘制变异图谱，将有助于了解ID的分子发病机制。
本研究旨在描述巴基斯坦近亲家庭中ID的遗传变异。
我们通过全外显子组测序（WES）分析了四个患有智力残疾的不相关巴基斯坦近亲家庭。使用不同的生物信息学工具和软件对数据进行分析。
我们在不同的ID基因中绘制了四个新的变异。每个变异都在不同的家庭中被发现，与隐性遗传模式共分离。发现的变异有：定位在FKRP基因中的c.1437delG:p.Asn480Thrfs*10，定位在HIRA基因中的c.2041 C>A:p.Leu681Met，定位在BDH1基因中的c.382 C>T:p.Arg128Cys，以及在TRAPPC6B基因中鉴定出的c.267+1G>A:p.?。
这些变异有助于证明巴基斯坦人群中智力残疾的状况和分子基础，从而提供遗传咨询服务，并为疾病变异数据库做出贡献。
