Fhad Abdulelah Almusharraf, Ahmed Rashed Alhomai, Abdulaziz Almugairin
Riyadh Schools, Riyadh, SAUDI ARABIA
Ataxia telangectasia like disorder (ATLD) is an autosomal recessive inheritance diseases, caused by mutations in Mre11 gene lead to deficiency of MRN complex protein. Clinically, ATLD patients show later onset of the neurological features, and slower progression. Recently, a new missense mutation, a G-to-C change at nucleotide 630 of the Mre11 gene, was described in a group of ATLD Saudi Arabian patients from three unrelated families. Aiming to investigate the cellular radiosensitivity of ATLD fibroblast cell strains against normal radiosensitive control and to assess the heterozygous carriers of G630C mutation in the general population. Cellular radiosensitivity was determined to three cell strains (wild type, ATLD homozygous, ATLD heterozygous), using the clonogenic survival assay. 434 Saudi nationals were studied. The 630 G / C mutation was genotyped by direct sequencing as same as Mre11 C18028T Mre11 C18216G SNPs. Survival curve showed extremely sensitive surviving fraction at 2GY of homozygous ATLD (SF2=0.07) cell strains and normal radiosensitivity for heterozygous ATLD (SF2=0.45) cell strains comparing to wildtype controls (SF2= 0.48).Two individuals with heterozygous G630C mutation were found giving a G/C genotype frequency of 0.5% and a mutant C allele frequency of 0.2%. Survival curves showed that ATLD heterozygote patient with cancer can receive safe and monitored radiation dose for adverse effects to treat their cancers. The allelic frequency indicates the presence of this rare mutation in our population. Pre-marital, pre-implementation, and prenatal screening for Mre11 G630C mutation could be useful to limit the risk of genetic diseases. Awards won at the 2010 ISEF Fourth Award of $500 - Team Projects - Presented by Intel