Thefragile X syndrome inalarge family. ICytogenetic andclinical investigations

SUMMARY Cytogenetic andclinical investigations were performed in85membersofa large family, inwhich18malesandsevenfemales were mentally retarded. Inthemalepatients the fragile site Xq27was foundin6to44% (mean22.5%)ofperipheral bloodlymphocytes. One non-retarded maleexpressed thecytogenetic abnormality in6% ofhiscells. In21females the fra(X) was foundin3to28%(mean8.7%)oftheir cells. Twoobligate carriers didnotexpress thefragile site. A significant difference inexpression between thesevenretarded (mean16-7%) andsevennon-retarded female carriers ofcorresponding age(mean6-3%) was found(a=0.01). Nosignificant correlation between expression andagecould beestablished, either inmalesorin females. Thecytogenetic results appeared tobeconsistent. Toavoidfalse positives, a cut-off point was chosen: males were considered tobefra(X) negative ifno more thanone in100cells showedtheabnormality; forfemales thecut-off point was twoin100cells. Segregation analysis didnotdetect significant deviations fromtheexpected ratios. Theputative presenceofa transmitting maleisdiscussed. Theresults ofrecombinant DNA analysis will bepublished elsewhere. Clinical investigations confirmed thefindings ofothers. CT scansshowed an enlargement oftheventricular systemthat exceeded theexpected agechanges.