title: Functional disomies of the X chromosome influence the cell selection and hence the X inactivation pattern in females with balanced X-autosome translocations: a review of 122 cases.
abstract: We reviewed 122 cases of balanced X-autosome translocations in females, with respect to the X inactivation pattern, the position of the X break point and the resulting phenotype. In 77% of the patients the translocated X chromosome was early replicating in all cells analysed. The break points in these cases were distributed all along the X chromosome. Most of these patients were either phenotypically normal or had gonadal dysgenesis, some had single gene disorders, and less than 9% had multiple congenital anomalies and/or mental retardation. In the remaining 23% of the cases the translocated X chromosome was late replicating in a proportion of cells. In these cells only one of the translocation products was reported to replicate late, while the remaining portion of the X chromosome showed the same replication pattern as the homologous part of the active, structurally normal X chromosome. The analysis of DNA methylation in one of these cases confirmed noninactivation of the translocated segment. Consequently, these cells were functionally disomic for a part of the X chromosome. The presence of disomic cells was highly prevalent in translocations with break points at Xp22 and Xq28, even though spreading of X inactivation onto the adjacent autosomal segment was noted in most of these cases. This suggests that selection against cells with a late replicating translocated X is driven predominantly by a functional disomy X, and that the efficiency of this process depends primarily on the position of the X break point, and hence the size of the noninactivated region.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Murdoch Institute, Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: D
authors.initials: D
authors.lastname: Du Sart
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D004171:Diploidy; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D010641:Phenotype; D014178:Translocation, Genetic / Q000235:genetics*; D014960:X Chromosome