Fragile X syndrome is resulted from an expansion of CGG repeat within FMR1 gene at the location q27.3 on the X chromosome. A repeat length over 200 CGGs leads to methylation of the repeat, which is accompanied by silencing of the FMR1 gene.

The silences the FMR1 gene and prevents expression of the fragile X mental retardation protein (FMRP), which is an RNA-binding protein. FMRP is involved in the expression of other genes and required for the normal development of connections between neurons.

Who should Take the Screening:

◆ Pre-pregnancy or early pregnancy

◆ Individuals with a family history of fragile X syndrome.

◆ Individuals with a family history of mental retardation, growth retardation, or autism.

◆ Individuals with infertility related to high follicle stimulating hormone (FSH) levels or premature ovarian failure (POF).

◆ Individuals with a family history of adult-onset ataxia or tremors.

■ Genotypes Associated with Fragile X Syndrome

• Unaffected：Normal FMR1 gene expression with no risk of children developing fragile X syndrome.

• Intermediate：Between unaffected and premutation; no risk of children developing fragile X syndrome, but increased risk of subsequent generations developing the syndrome.

• Premutation：Abnormal FMR1 gene expression; no symptoms or mild symptoms, but increased risk of children developing fragile X syndrome.

• Full mutation：Abnormal FMR1 gene expression with obvious symptoms of Fragile X syndrome and a high risk of children developing fragile X syndrome.

■FMR1 CGG repeat size
Normal: 5 to 44 repeats
Intermediate: 45 to 54 repeats
Premutation: 55 to 200 repeats
Full mutation: More than 200 repeats

■ Genetic Model of X-linked Dominant

X-linked dominant inheritance results can lead to two outcomes in babies:

1. A mother who is a carrier of Fragile X has a 50% chance of passing the mutated gene to each of her children.

2. A father who is a carrier of Fragile X has a 100% chance of passing the mutated gene to his daughter; however, his son will be normal.

Step 1. Consult a physician and a genetic counselor before completing the consent form.

Step 2. 2~3 c.c. blood sample is collected and couriered to the SOFIVA laboratory.

Step 3. Perform PCR to amplify the FMR1 gene following DNA extraction.

Step 4. Perform analysis to determine the number of CGG sequence repeats and the degree of methylation.

Step 5. Physician explains fragile X syndrome report.

Note: Males suspected of having the full mutation genotype should undergo methylation analysis for confirmation.