Genetic Mutations of Intellectual Disability in Iranian Families with Consanguinity and Normal Karyotype Using Whole Exome Sequencing

Background and Objective: Intellectual disability is a lifelong disorder with a prevalence of ۲-۳%, and today, only half of the patients receive a diagnosis. The causes of intellectual disability disorders are heterogeneous and include environmental factors as well as genetic factors. The primary cause of intellectual disability is predominantly of genetic origin. There is substantial evidence indicating that the use of Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS) in clinical settings improves the diagnosis and treatment of genetic diseases.Materials and Methods: In this study, ۱۰ families from different regions of Iran with children affected by intellectual disability were examined after obtaining consent, completing questionnaires, and constructing pedigrees. After assessing the quality of the extracted DNA, samples were sent to Kavosh Gene Company for Whole Exome Sequencing (WES). Sequencing was performed using the Illumina device with the Nexseq ۲۰۰۰ platform and ۱۰۰-base pair reads. The results, after initial filtering, were interpreted using software and websites such as Ensembl, Franklin, Varsome, and Mutation Taster.Findings: According to the results, mutations in the genes TSEN۵۴, FGFR۲, KCNMA۱, KMT۲C, SCN۲A, SCN۱A, and MAN۲C۱ were consistent with the patients' phenotypes. Among the mutations identified from the WES data, two types Pathogenic and Likely Pathogenic had greater diagnostic significance.Conclusion: In this study, variants from the mentioned genes were found in the probands, and after Sanger Sequencing, these variants were confirmed to match the clinical symptoms of the patients. The exome sequencing technique helped reduce the number of idiopathic cases in intellectual disability disorders. Additionally, after identifying the mutations, they can be used for diagnosis in consanguineous marriages, as well as for pre-implantation and prenatal testing.

کلیدواژه ها:

Whole exome sequencing ، Intellectual disability ، Pedigree ، Normal karyotype ، siRNAs ، miRNAs