Clinical and cytological aspects of sex chromosome activity.

Abstract

The first known example of a human female with more than one euchromatic X chromosome in somatic cells is presented, viz. a child with 2 normal X chromosomes and the long arm of a third X translocated onto one of the No. 22 chromosomes. In cultured lymphocytes there occurred, in addition to the ordinary Lyon pattern of X chromosome inactivation, 2 other patterns in which (1) 2 normal X chromosomes, and (2) one X and the t(X;22) were euchromatic. As the inactivation within the translocation chromosome did not spread onto chromosome 22, the clinical symptoms of the child had to be attributed to the excess of active X material, not to monosomy 22. Contrary to this, absence of heterochromaty of the Y chromosome does not influence the phenotype, as shown by the case of mixed gonadal dysgenesis with non-fluorescing Y presented. Possible reasons for this difference include: (1) The differences between facultative X and constitutive Y heterochromatin; (2) Different cytologic criteria for heterochromatin may not mean the same kind of inactivity; (3) Differences in phenotypic expression may be due to different chromosomal behaviour among tissues; (4) Late replication and decondensation may not equate genetic inactivity in terms of transcriptional inactivity.