The fragile X syndrome in a selected population of mentally retarded individuals

Abstract

Fragile X syndrome is the most common heritable cause of mental retardation with a prevalence of 1 in 4000 males. Individuals effected present with mental retardation or learning disabilities and typically have a long face, prominent jaw and in post-pubertal males, enlarged testis. The syndrome segregates as an X-linked dominant disorder with reduced penetrance. Either sex when carrying the mutation may exhibit mental deficiency. The syndrome has been associated with an expansion mutation involving CGG repeats in the FMRl gene situated at Xq 27.3. Normal individuals have 6-45 CGG repeats, carriers have 56-200 triplets (premutation) and effected individuals have more than 200 CGG triplets (full mutation). Alleles with 46-55 repeats are in the grey zone and the risk of expansion has not been clearly defined. The premutation may be transmitted through both males and females. This study presents a local screening programme on a selected population of mentally retarded individuals. Aims: To identify and characterise children with familial mental retardation in special schools for the mentally retarded. Materials and Methods: In this study mentally retarded children and adolescents from three special schools were screened. DNA obtained from buccal cells was analysed using the polymerase chain reaction to amplify the CGG region and assess its size. Parental consent was obtained from seventy mentally retarded individuals and these were screened. Results: Two boys (maternal first cousins) had a methylated full mutation; one girl was a premutation carrier; three boys and one girl had alleles in the grey zone. Family history in all these cases was negative. Two further boys from normal schools tested because of a family history of familial mental retardation were mosaics for a premutation and a full mutation.