Fragile X Syndrome
Related Gene(s): FMR1
Fragile X syndrome affects approximately 1 in 1250 males and 1 in 2000 females, making it the single most common form of inherited mental retardation. It is caused by expansion of the trinucleotide CGG repeat in the 5’ untranslated portion of the FMR1 gene on the X chromosome. Normal individuals have between 2-44 copies of repeat. In some individuals, the number of trinucleotide repeat units is increased to between 55 and 200, known as a premutation.
Females carrying a premutation are at risk for their allele to expand to a full mutation. Full mutations (>200 repeats) lead to full expression of the clinical and cytogenetic phenotype. Alleles between 44 and 55 repeats are inconclusive (intermediate) such that some alleles are stable and some are unstable. To date, no allele with fewer than 56 repeats has been reported to expand to a full mutation in a single generation.
The American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics recommend that carrier screening for fragile X syndrome be offered to women with a family history of fragile X syndrome or undiagnosed mental retardation before or during pregnancy. In addition, ACOG recommends that screening be offered to women with a family history of developmental delay, autism, or premature ovarian insufficiency. Carrier screening for fragile X syndrome may be considered for any woman before or during pregnancy.
To detect all possible alleles, both PCR amplification and Southern blot analyses are performed. In rare instances, mutations in the coding region can cause fragile X syndrome. In such cases, sequencing of the FMR1 gene is performed in addition to trinucleotide repeat analysis.
Prenatal diagnosis is also available. Prior to ordering prenatal testing, please contact our laboratory at 212-241-7518 to discuss.
- Chorionic villi: 5-10 mg in conical tube with sterile saline or transport media
- Amniotic fluid: 15 mL in conical tube
- Cultured cells: Two confluent T-25 flasks
- Additionally, please send:
- Maternal blood: 5-10 mL in EDTA tube (lavender top) required to perform MCC studies on all prenatal samples and in case maternal confirmation studies are necessary
- For adults
- Blood: Two 5-10 mL tubes with EDTA (lavender top) or two 5-10 mL tubes with ACD (yellow top) from the patient.
- For newborns or children
- Blood: 2 mL in pediatric EDTA tube (lavender top) or 2 mL in pediatric ACD tube (yellow top) from patient
- Ship at room temperature
- 10-14 days
Comprehensive Jewish Carrier Screening