A population study of FMR1 mutations in Malta

Abstract

The fragile X Syndrome is the most common inherited form of mental retardation. The commonest mutation is an expansion of the unstable (CGG)n sequence in the 5'UTR exon of the FMR1 gene situated at Xq27.3. This study describes the results of testing for the mutation in the FMR1 gene among mentally retarded individuals attending the special schools for mentally retarded in Malta and a group of mentally retarded boys attending the normal schools referred for genetic analysis. Testing was done using molecular biological techniques on buccal DNA as well as on blood Iymphocytes. The most suitable method was the polymerase chain reaction using appropriate primers and a 7 -deaza dGTP to enable visualisation of larger premutations. A total of 99 individuals in the special schools were selected for testing, 65% consented and 65 individuals were tested. Among these, 2 males with full mutations, 1 female carrying a premutation and 4 individuals with grey-zone alleles were identified. Among 23 boys referred for testing, 3 full mutations were identified. This study showed that PCR testing on DNA extracted from buccal cells is a sensitive technique, useful as a noninvasive screening procedure. It is suggested that a continuation of clinical screening and buccal cell PCR be used for the detection of fragile X mutation in children with mental retardation in normal schools. Suggestions for future studies and a protocol for estimating the prevalence of fragile X syndrome are put forward.