What genetic testing options are available for confirming a diagnosis of Fragile X Syndrome in suspected cases?

Genetic testing for confirming a diagnosis of Fragile X Syndrome (FXS) primarily involves analysis of the FMR1 gene to detect CGG trinucleotide repeat expansions. The standard and most reliable test is PCR-based testing combined with Southern blot analysis, which quantifies the number of CGG repeats and detects methylation status, crucial for diagnosing full mutations (>200 repeats) that cause FXS NICE CG71.

PCR testing alone is effective for identifying normal and premutation alleles (55-200 repeats), but Southern blot remains essential to confirm full mutations and methylation patterns, especially in cases with mosaicism or borderline repeat numbers. This combined approach ensures accurate diagnosis in suspected cases NICE CG71.

Recent literature supports this approach and highlights the importance of comprehensive FMR1 testing for both diagnosis and genetic counseling, emphasizing that molecular testing guides clinical management and family planning decisions McConkie-Rosell et al. 2005. Additionally, advances in PCR techniques have improved sensitivity and reduced turnaround times, but Southern blot remains the gold standard for full mutation confirmation Elhawary et al. 2023.

In summary, the recommended genetic testing options for confirming Fragile X Syndrome are PCR screening for CGG repeat sizing followed by Southern blot analysis for full mutation and methylation status confirmation, aligning with UK clinical practice and supported by current research.