Genetic abnormality’ in fragile X-syndrome: (PGI June 2007)
**Core Concept**
Fragile X syndrome is a genetic disorder caused by an expansion of a CGG repeat in the FMR1 gene on the X chromosome, leading to the silencing of the gene and subsequent deficiency of the FMRP protein. This protein plays a crucial role in synaptic plasticity and neuronal development.
**Why the Correct Answer is Right**
The correct answer involves the expansion of a CGG repeat in the FMR1 gene. This repeat expansion leads to the formation of a methylated and heterochromatinized region that silences the gene. As a result, the FMR1 gene is not expressed, and the FMRP protein is deficient. The FMRP protein is essential for normal neuronal development and function, and its deficiency leads to the characteristic features of fragile X syndrome.
**Why Each Wrong Option is Incorrect**
* **Option A:** This option is not related to the genetic abnormality in fragile X syndrome. Trinucleotide repeat expansions are indeed associated with several neurodegenerative disorders, but the specific CGG repeat expansion in the FMR1 gene is unique to fragile X syndrome.
* **Option B:** This option is incorrect because the FMR1 gene is located on the X chromosome, and the expansion of the CGG repeat leads to the silencing of the gene, not its overexpression.
* **Option C:** This option is not relevant to the genetic abnormality in fragile X syndrome. The FMR1 gene is not associated with the development of cancer, and the expansion of the CGG repeat does not lead to oncogenic mutations.
**Clinical Pearl / High-Yield Fact**
The CGG repeat expansion in the FMR1 gene is a classic example of a trinucleotide repeat disorder, which is a type of genetic mutation that can lead to a range of neurodegenerative and developmental disorders.
**Correct Answer: C. CGG repeat expansion in the FMR1 gene.**