Assessment of Carriers' Frequency of a Novel MRE11 Mutation Responsible for the Rare Ataxia Telangiectasia-Like Disorder

摘要

Ataxia telangiectasia-like disorder (ATLD) is a very rare variant of ataxia telangiectasia. ATLD is caused by mutations in MRE11 gene. Recently, a new missense mutation, a G-to-C change at nucleotide 630 of the MRE11 gene, was described in 10 ATLD Saudi Arabian patients from three unrelated families. This is the biggest ATLD group of patients that may suggest noticeable heterozygous carriers of G630C mutation in the general population. The aim of the present study was to assess the allelic frequency of this mutation. A cohort of 428 Saudi nationals was studied. The 630G > C mutation was genotyped by direct sequencing. 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%. This indicates the presence of this rare mutation in our population with heterozygous carriers' frequency of 0.5%. The frequency could be higher in geographically isolated families with high consanguinity. Premarital, preimplementation, and prenatal screening for MRE11 G630C mutation could be useful to limit the risk of genetic diseases.