Which neurodevelopmental disorder is caused by CGG trinucleotide expansion on the X chromosome affecting the FMR1 gene?

Which neurodevelopmental disorder is caused by CGG trinucleotide expansion on the X chromosome affecting the FMR1 gene?

• A. PKU
• B. Red-green color blindness
• C. Tay-Sachs disease
• D. Fragile X syndrome

Answer: (D)

Fragile X syndrome is caused by an abnormal expansion of CGG trinucleotide repeats in the FMR1 gene on the X chromosome. This expansion triggers hypermethylation and silencing of FMR1, leading to a deficiency of the FMRP protein that regulates synaptic development and plasticity. The result is a neurodevelopmental disorder characterized by intellectual disability, learning and behavioral challenges, and features often seen in autism; males are typically more severely affected due to having only one X chromosome, while females show a wider range of severity because of X-inactivation. The repeat length also influences severity and can expand in future generations (anticipation).

Fragile X syndrome is caused by an abnormal expansion of CGG trinucleotide repeats in the FMR1 gene on the X chromosome. This expansion triggers hypermethylation and silencing of FMR1, leading to a deficiency of the FMRP protein that regulates synaptic development and plasticity. The result is a neurodevelopmental disorder characterized by intellectual disability, learning and behavioral challenges, and features often seen in autism; males are typically more severely affected due to having only one X chromosome, while females show a wider range of severity because of X-inactivation. The repeat length also influences severity and can expand in future generations (anticipation).