Molecular fragile X screening in normal populations

Area of Science:

• Genetics
• Reproductive Medicine
• Molecular Diagnostics

Background:

• Fragile X syndrome (fraX) is a leading inherited cause of intellectual disability.
• Prenatal and preconceptual genetic screening are crucial for reproductive health.
• Limited data existed on patient acceptance of fraX carrier testing in routine counseling.

Purpose of the Study:

• To assess the feasibility and patient acceptance of offering DNA fragile X (fraX) carrier testing.
• To evaluate the prevalence of fraX carriers in pregnant women and egg donors.
• To determine the utility of fraX testing in genetic counseling settings.

Main Methods:

• A pilot project offered DNA fraX testing to pregnant women and anonymous egg donors.
• Patients received educational brochures prior to counseling sessions.
• DNA analysis involved Southern blot and PCR-based methods to determine CGG repeat sizes.

Main Results:

• Out of 3,345 women offered testing, 474 with no family history accepted; three carriers (CGG repeat sizes = 60+) were identified.
• None of the 214 women with a positive family history were found to be carriers.
• Two high borderline cases (repeat sizes 50-59) were identified among 271 egg donors.

Conclusions:

• DNA fragile X carrier screening is accepted by patients in routine prenatal and genetic counseling.
• The study highlights the importance of offering fraX testing to identify carriers, even with no family history.
• FraX carrier screening is a valuable addition to current reproductive medical practices.