No abstract

Fragile X syndrome (FXS) is the commonest cause of inherited mental retardation and clinically presents with learning, emotional and behaviour problems. FXS is caused by expansion of cytosine-guanine-guanine (CGG) repeats present in the 5’ untranslated region of the FMR1 gene. The aim of this study was to screen children attending special education institutions in Sri Lanka to estimate the prevalence of CGG repeat expansions. The study population comprised a representative national sample of 850 children (540 males, 310 females) with 5 to 18 years of age from moderate to severe mental retardation of wide ranging aetiology. Screening for CGG repeat expansion was carried out on DNA extracted from buccal cells using 3’ direct triplet primed PCR followed by melting curve analysis. To identify the expanded status of screened positive samples, capillary electrophoresis, methylation specific PCR and Southern hybridization were carried out using venous blood samples. Prevalence of CGG repeat expansions was 2.2%. Further classification of the positive samples into FXS full mutation, pre-mutation and grey zone gave prevalence of 1.3%, 0.8% and 0.1% respectively. All positive cases were male. No females with FXS were detected in our study may have been due to the small sample size.

Introduction: Fragile X syndrome (FXS) is the commonest inherited cause of intellectual disability. Children with FXS usually present clinically with developmental, learning and behavioural disorders. Physical characteristics of FXS are well documented and are considered a primary guide to recognition. Genetic screening for FXS targets the detection of cytosine-guanine-guanine (CGG) triplet repeats in the FMR1 gene on the X chromosome. Objective: Aim was to estimate the frequency, clinically and genetically, in children referred to a specialist child mental health clinic for preschool and school based learning difficulties. Design and method: A total population of children referred to a specialist mental health service for learning difficulties during a specified period was screened clinically and genetically for FXS. Clinical diagnosis was based on known physical characteristics. They were further assessed on cognitive functions, learning and behaviour. Optimised and validated conventional polymerase chain reaction (PCR) amplification was used for genetic screening where deoxyribonucleic acid (DNA) for the assay was obtained from buccal cells. Results: The total sample studied was 286 children, 4-12 years of age. Based on morphological features, 5.9% received the diagnosis of FXS and one child was genetically positive. Of the rest, 2 more children were genetically positive but clinically negative.

Among the special school attendees, prevalence of FXS was 1.3% which has a high risk for autism and attention deficit hyperactivity disorder.