Implementation of a technique to find out genetic variants on X-linked mental retardation (XLMD) in the Sri Lankan patient cohort

Abstract

Introduction: A person is considered intellectually disabled (ID) if an intelligence quotient less than 70-75. Mental retardation (MR) found in ~1-3% of the population, impacting the lives of affected individuals and their families. Approximately 30% of more males with ID having effected X-chromosomal genes. Genetic causes accounted for 38.5% of all cases of intellectual disability. Aristaless related homeobox ARXgene, is Frequently mutated causing X-linked intellectual disability (XLID). The objective of the study was to design and implement a PCR assay for detection of pathogenic variants in the ARX gene (ARX T>C; rs28936077) associated with XLMD. Methods: A comprehensive literature review was conducted to determine the association of genetic variants in XLMR.A tetra-amplification refractory mutation system polymerase chain reaction (T-ARMS PCR) was designed for the ARX T>C; rs28936077genetic variant. The designed assay was optimized and validated by Sanger sequencing, using the DNA of 14 venous blood samples, that were obtained from a cohort of patients with mental retardation who had given prior informed consent for such studies. Results: The genotypic frequencies for the normal variants were 100%. There were no heterozygotes or homozygotes for the pathogenic variant in the current study cohort. Conclusion: Designing, optimization and implementation of the tetra-amplification refractory mutation system polymerase chain reaction (T-ARMS PCR), as a novel PCR assay was successful and can be used as a diagnostic tool to detect the presence of ARX T>C; rs28936077genetic variants in patients with mental retardation. Further studies should be conducted on larger study cohort to determine the allele frequency of the Sri Lankan population.