CGG

CGG refers to a specific trinucleotide sequence composed of cytosine, guanine, and guanine. In the genetic code, CGG is a codon that specifies the amino acid arginine in messenger RNA translation; in DNA, the triplet CGG serves as the same sequence of bases. Repeats of the CGG trinucleotide can occur in various genes, but the most extensively studied example is in the FMR1 gene on the X chromosome.

Fragile X syndrome arises when CGG repeats in the FMR1 gene's regulatory region expand beyond a threshold of about 200 repeats. This expansion leads to hypermethylation and silencing of the FMR1 gene, reducing or eliminating the production of the FMRP protein, which is involved in synaptic development and function. The number of repeats correlates with phenotype and inheritance risk. Categories used by clinicians typically include normal (roughly 5–44 repeats), intermediate or gray zone (around 45–54 repeats), premutation (55–200 repeats), and full mutation (more than 200 repeats). Premutations are associated with Fragile X–associated disorders, such as Fragile X–associated tremor/ataxia syndrome (FXTAS) in adults and premature ovarian insufficiency in females; full mutations cause intellectual disability and other features.

Diagnosis relies on molecular genetic testing, typically using polymerase chain reaction (PCR) to count smaller repeats and Southern blot analysis for larger expansions. Counseling considers transmission risk, as premutations can expand to full mutations in subsequent generations, with implications for affected individuals and families. CGG repeats and their expansion dynamics remain a key focus in clinical genetics and neurodevelopmental research.