Table of contentsIntroductionMethod:Study populationWhole exome sequencingIn silico analysisSanger sequencingResult:Family descriptionBirth history of children in the familyCommon patient characteristicsWhole exome sequencingExome sequencing entire candidateTesting for GPT2 mutations in the familyIntroductionIntellectual disability (ID) is a disease of the central nervous system that affects 2 to 3% of the world's population. With a wide range of signs and symptoms, three major criteria constitute the diagnostic picture of intellectual disability: an intelligence quotient (IQ) below 70, symptoms present before the age of 18 and deficits in at least two behaviors adaptive [Prada 2016; Celis 2015].Say no to plagiarism. Get a tailor-made essay on “Why Violent Video Games Should Not Be Banned”? Get an original essay. This clinically heterogeneous disorder may develop due to genetic and/or environmental causes. The genetic risk factor, de novo or hereditary, is considered responsible for 25 to 50% of these cases and this rate increases with the severity of the ID [Prada 2016; Kaufmann 2010; Célis 2015]. From this point of view, ID can be classified into syndromic and non-syndromic forms. Although more than 450 unique candidate genes have been identified for Mendelian ID, the cause of the disease remains unknown in half of cases [Kaufman 2010]. The development of DNA sequencing technology over the past decade has marked a dramatic era for the discovery of the genetic etiology of ID. More than thirty studies have been performed to provide occasional variants in various families, including sporadic or familial cases [Rabbani2014]. For example, Najmabadi et al. reported 50 new candidate genes in 136 Iranian families [Najmabadi 2011]. While about 1% of the genome (30 MB) (~3 to understand the genetic pathology of such a clinically heterogeneous disorder. Using [WES/Trio WES], we detect a novel variant of the GPT2 gene that influences all affected siblings of an Iranian family in a homozygous mutation. Method: Study population The proband was 23 years old. boy from a semi-large Iranian family, who had three affected sisters and three healthy sisters. He suffered from an intellectual disability without any malformation. After obtaining signed informed consent from the parents, a complete clinical evaluation carried out by the referring doctor as well as the recording of the family pedigree by the geneticists of our team. This study has ethical approval from AJA University of Medical Sciences Tehran, Iran (code: ???) Whole exome sequencing Briefly, after blood sample preparation, DNA extraction, enrichment of genomic DNA fragments by > 340,000 probes designed against the human genome (Nextera Rapid Capture Exome, Illumina); Library preparation on an Illumina NextSeq or HiSeq 4000 platform (Illumina) was performed at an average coverage depth of 70-100X. In the Silico analysis, based on the family inheritance mode, a multi-step filtering strategy was applied to reduce the identified variants to a small number. Application of public databases such as 1000 Genome Project, dbSNP, ClinVar, SIFT, Polyphen, Mutation Taster Software and in-house databases (Iranome) to reach originally possible variants. The Sanger SequencingCandidate variant was confirmed using bidirectional direct sequencing for the entire family. (Details,.