A 20-year-old with a long face and large testes has expanded CGG repeats in the FMR1 gene. What is the most likely effect of these repeats on FMR1 mRNA transcription?

• A. Alteration of mRNA splicing
• B. Decreased transcription
• C. Enhancement of mRNA degradation
• D. Incorporation of CGG repeats into mRNA

Answer: (B)

The presence of expanded CGG repeats in the FMR1 gene is characteristic of Fragile X syndrome. In this condition, the long repeats lead to hypermethylation of the promoter region of the FMR1 gene, which inhibits gene transcription. As a result, the overall production of FMR1 mRNA decreases significantly.

This decrease in transcription is a crucial aspect of the pathophysiology of Fragile X syndrome, as it leads to insufficient production of the fragile X mental retardation protein (FMRP), which is essential for normal neural development and synaptic function. In this case, the large number of CGG repeats serves to effectively silence the gene, rather than modifying splicing or causing other changes to mRNA. This altered expression ultimately contributes to the symptoms observed in individuals with the disorder, including developmental delays and characteristic physical features.