Molecular genetics of Turner's syndrome

Recombinant DNA technology now allows an analysis of sex chromosomal abnormalities at the molecular level. X chromosomes differ in respect of their pattern of cutting sites for particular restriction enzymes; these differences can be used to determine which X chromosomes or which part of an X chromosome has been inherited from a parent. Furthermore, these techniques can be used to define the presence or absence of particular regions of the X chromosomes with a higher level of resolution than it is possible to achieve using light microscopy. Thirty-eight families in which there was a child or fetus with Turner's syndrome were studied using a series of DNA probes that detect differences (restriction fragment length polymorphisms) among X chromosomes. Analysis of the origin of the normal X chromosome was possible in 27 families. In 14 families with 45,X the observed X was maternal in each, whereas in 13 children with other karyotypes (46,X,i(Xq); 45,X/46,X,i(Xq); 45,X/46,XX; 45,X/46,X,r(X)) the origin of the normal X was paternal in six and maternal in seven patients. In two other families, mosaicism, which was unsuspected at chromosomal analysis, was revealed. DNA probes studied in the remaining nine families were uninformative. These results suggest that different pathogenic mechanisms operate for pure 45,X when compared with the other karyotypes associated with Turner's syndrome. The presence of unsuspected mosaicism in some of these families has clinical implications in relation to prognosis and management.