What is the association of trinucleotide repeats in fragile X and its transmission pattern?

The association of trinucleotide repeats in fragile X syndrome is characterized by anticipation, where there is an increase in repeat number across generations. This phenomenon occurs due to unstable expansions of the CGG trinucleotide repeat in the fragile X mental retardation 1 (FMR1) gene.

In individuals who are carriers, especially females, there can be a range of repeat numbers. When passed from a carrier mother to her offspring, the repeats can expand, leading to a higher number of repeats in the subsequent generation. This incremental increase in repeat length can lead to more severe manifestations of the condition, such as intellectual disabilities, in affected individuals.

This unique transmission pattern, where the severity of symptoms potentially worsens with each generation, distinguishes it as a classic example of genetic anticipation in trinucleotide repeat disorders. Understanding this mechanism is crucial for genetic counseling and management in families affected by fragile X syndrome.