FMR1 Gene Mutation Analysis and CGG Repeat Number Distribution from a Single Center

Abstract

Background: Mutation occurring in fragile X mental retardation 1 (FMR1) gene is acknowledged as the most common cause for X chromosome linked intellectual disability/mental retardation (XLID/XLMR). This gene harbors unstable CGG triplet repeats within its 5'UTR (untranslated region). Loss of function of the FMR1, which is mostly due to the hypermethylation of the CpG islands on its promoter region, causes fragile X syndrome (FXS). Displaying different frequencies, the FXS is a common phenomenon all over the world, the studies focus mostly on the Caucasian population. Purpose: We aimed to reveal the CGG repeat number distribution and the mutation profile of the FMR1 gene in clinically pre-diagnosed FXS patients and in family members of the patients who were diagnosed as full mutation. Methods: We evaluated the copy number of the CGG triplets in 767 FXS patients and their family members in Antalya province by employing fragment analysis molecular technique. We also assessed, by segregation analysis, whether there is unusual genetic transmission pattern of CGGs. Results: The molecular analysis shows the most common copy numbers of CGGs are thirty, twenty-nine and thirty-one. Present study is the first report concerning Antalya city of Turkey about the frequencies of the normal CGG repeats number, grey-zone, pre-mutation and full mutations, we updated our molecular test results with two unusual transmittance patterns of the CGG repeats. Conclusion: Since the potential of CGG repeat properties may cause differential intergenerational transmission patterns, its' population specific evaluation can contribute to provide a better genetic diagnosis and genetic counseling services for the related clinical entities.