L�ri-Weill syndrome associated with a pseudodicentric X;Y translocation chromosome and skewed X-inactivation: Implications for genetic counselling

A female patient of normal intelligence with short stature and Madelung deformity is reported with Leri-Weill dyschondrosteosis and a de novo pseudodicentric X;Y translocation chromosome. The phenotype is consistent with the observed deletion of the SHOX gene by FISH and molecular studies. The Y chromosome breakpoint was in the short arm but proximal to SRY, consistent with her phenotypic sex. X-inactivation studies have shown a skewed pattern in favour of the dic (X;Y) chromosome. The ARSE gene was also deleted on the dic (X;Y) chromosome but chondrodysplasia punctata was not expressed, as CDP is recessive and ARSE escapes inactivation on the normal X chromosome. Breakpoint mapping assisted in karyotype/phenotype correlation and reproductive counselling. In particular, molecular analysis showed that the putative MRX 49 gene for mental retardation is unlikely to be deleted in this case.