DNA TESTING FOR FRAGILE-X SYNDROME IN SCHOOLS FOR LEARNING-DIFFICULTIES

Fragile X syndrome is the most common inherited cause of mental retard ation. Early diagnosis is important not only for appropriate managemen t of individuals but also to identify carriers who are unaware of thei r high risk of having an affected child. The disorder is associated wi th a cytogenetically visible fragile site (FRAXA) at Xq27.3, caused by amplification of a (CGG)(n) repeat sequence within the gene at this l ocus designated FMR1. Clinical and molecular studies have been underta ken to screen for fragile X syndrome in 154 children with moderate and severe learning difficulties of previously unknown origin. Southern b lot analysis of peripheral blood showed the characteristic abnormally large (CGG), repeat sequence associated with fragile X syndrome in fou r of the 154 children. The findings were confirmed by cytogenetic obse rvation of the fragile site and by further molecular studies. The fami lies of the affected children were offered genetic counselling and DNA tests to determine their carrier status. These findings show that the re are still unrecognised cases of fragile X syndrome. Given the diffi culty of making a clinical diagnosis and the implications for families when the diagnosis is missed, screening in high risk populations may be justified. The issues involved in screening all children in special schools for fragile X syndrome are discussed.