A 30-Year Experience in Fragile X Syndrome Molecular Diagnosis from a Laboratory in Thailand

Abstract

Fragile X syndrome (FXS) is the most common form of X-linked intellectual disability (ID). This study aimed to share 30 years of experience in diagnosing FXS and determine its frequency in Thailand. We retrospectively reviewed 1480 unrelated patients (1390 males and 90 females) with ID, developmental delay, or autism spectrum disorder, or individuals referred for FXS DNA testing at Songklanagarind Hospital, Thailand, over a 30-year period. The samples were analyzed using cytogenetic methods, PCR-based techniques, and/or Southern blot analysis. Full mutations (>200 CGG repeats) were identified in 100 males (7.2%) and three females (3.3%). An intermediate allele was detected in one male, while no premutation was found in the index cases. Two males were suspected to have FMR1 gene deletions. Twelve families underwent prenatal testing during this study. Most families undergoing prenatal FXS diagnosis involved mothers who were premutation carriers and had given birth to children affected by FXS. This study represents the largest series of molecular genetic FXS testing cases reported in Thailand. The frequency of FXS identified in different cohorts of Thai patients across various periods was approximately 7%. This study enhances public awareness of at-risk populations and highlights the importance of prenatal testing and genetic counseling for vulnerable families.

Keywords: FMR1; fragile X syndrome; full mutation; molecular diagnosis.

Figure 1

Frequencies of FXS in different high-risk populations. The frequency of fragile X full mutation varies across populations. The frequencies of FXS in different cohorts of Thai patients during various periods were approximately 7%. F, female; M, male.

Figure 2

Summary of the techniques used for FXS diagnosis in Thailand during this study period, from 1991 to the present. FXS testing in this study was performed using cytogenetic analysis (1991–1996) and molecular techniques (1996–present). TP-PCR, triplet-repeat-primed PCR; msTP-PCR, methylation-specific triplet-primed PCR.