# Detection of FMR1 CGG Repeat Expansions Using Buccal Swab and Blood Samples of Children With Intelectual Disability in A Resource-Limited Country

## TL;DR

This study compares blood and buccal swab samples for detecting Fragile X Syndrome in children with intellectual disabilities in Indonesia, finding that buccal swabs are a viable non-invasive alternative.

## Contribution

The study demonstrates that buccal swabs can be used effectively for FXS screening in resource-limited settings, offering a non-invasive alternative to blood samples.

## Key findings

- Buccal swab and blood samples showed perfect concordance in conventional PCR for FXS detection.
- Buccal swabs revealed DNA quality issues in TP-PCR MCA, indicating a need for optimization.
- FXS prevalence among the studied children was 1.22%.

## Abstract

•Comparison of FXS testing using blood and buccal swab in children with ID.•Conventional PCR and TP-PCR MCA methods applied to analyze CGG repeat expansion.•Buccal swab shows promising concordance with blood in conventional PCR.•Non-invasive sampling method offers feasible alternative for genetic screening.•Study supports wider use of buccal swabs in FXS diagnosis among children with special needs.

Comparison of FXS testing using blood and buccal swab in children with ID.

Conventional PCR and TP-PCR MCA methods applied to analyze CGG repeat expansion.

Buccal swab shows promising concordance with blood in conventional PCR.

Non-invasive sampling method offers feasible alternative for genetic screening.

Study supports wider use of buccal swabs in FXS diagnosis among children with special needs.

Fragile X Syndrome (FXS), the most common inherited intellectual disability, is caused by CGG-repeat expansions in the FMR1 gene. In resource-limited settings such as Indonesia, the absence of systematic screening programs complicates early detection. This study compared the performance of buccal swab and blood samples in detecting FMR1 repeat expansions to facilitate non-invasive screening. A total of 164 male students with intellectual disabilities in Jakarta provided paired buccal swab and blood samples. Conventional PCR was used for initial screening, followed by Triplet-Primed PCR (TP-PCR) with Melt Curve Analysis (MCA) and sizing confirmation by fluorescent TP-PCR and capillary electrophoresis. Conventional PCR identified 159 normal alleles, three grey zones, and two full mutations, resulting in an FXS prevalence of 1.22 %. A perfect concordance was observed between buccal swab and blood samples (Cohen’s Kappa = 1.000). Additional TP-PCR MCA analysis on 80 selected samples revealed inconsistencies in buccal swab results, with 12 cases classified as indeterminate, suggesting potential DNA quantity and/or quality issues. These findings indicated that buccal swabs are a feasible, non-invasive sampling method to screen FXS via conventional PCR, though further optimization is required for TP-PCR MCA. This study represents the first FXS screening in Jakarta, emphasizing the importance of early detection and scalable genetic testing strategies, particularly in resource-limited settings.