Fragile X molecular investigation and genetic counseling of intellectual disability/developmental delay patients in an Indian scenario.

Background: Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability (ID), is caused by a CGG repeat expansion (full mutation (FM), >200 CGG) at the Fragile X Mental Retardation 1 (FMR1) gene. Early identification of FXS has prognostic significance for affected individuals due to early initiation of interventions. Genetic counseling and family screening can aid parents and at-risk asymptomatic carriers (premutation (PM), 55-200 CGG) in taking proper reproductive decisions. Methodology: The present study utilizes Triplet Primed-Polymerase Chain Reaction (TP-PCR) methodology for detecting the repeat expansion at FMR1 gene in 233 Indian intellectual disability/developmental delay (ID/DD) patients. Results: We have identified 18/233 (7.7%) FXS positive cases. Early diagnosis was made in 66.7% cases (<10 years). Extended family screening in 14 affected individuals identified 9 additional FM cases (7 males and 2 females) and 23 carrier PM females, which otherwise could have been missed. Four prenatal diagnoses were also performed, leading to the identification of 1 PM and 1 FM carrier fetus. Conclusion: A high frequency (7.7%) of FXS among Indian ID/DD subjects obtained in this study depicted the need for more professional recommendations concerning prompt referral for genetic testing, and increased exposure to information about FXS to pediatricians.