Are We Ready for Fragile X Newborn Screening Testing?-Lessons Learnt from a Feasibility Study.

Area of Science:

• Genetics
• Molecular Biology
• Public Health

Background:

• Fragile X syndrome (FXS) is a leading genetic cause of cognitive impairment.
• Current newborn screening (NBS) programs in Australia do not include FXS.
• Assessing FXS screening feasibility is crucial for early intervention.

Purpose of the Study:

• To evaluate the feasibility and reliability of population-based FXS screening.
• To test a modified PCR assay using routine NBS dried blood spot samples.
• To determine the cost-effectiveness of FXS screening.

Main Methods:

• A pilot study involving 1971 mothers and 2000 newborns.
• DNA extraction from routine NBS dried blood spots.
• Modified PCR assay with a chimeric CGG primer, validated against a routine PCR assay.

Main Results:

• The chimeric primer assay accurately detected fragile X alleles (normal, premutation, full mutation).
• Complete concordance was observed between the chimeric and routine PCR assays.
• The cost per test was $AUD19, with 10 cases of premutation alleles identified.

Conclusions:

• Fragile X status can be determined from routine NBS samples using the chimeric primer assay.
• The assay's cost-effectiveness for population screening is questionable.
• Consideration as a second-tier assay to an FMRP immunoassay may be viable.