X chromosomes attached by their short arm : presence of an inactive centromere influences the replication patterns

A 19 years old girl with gonadal dysgenesis and short stature had one giant chromosome formed by two X-chromosomes attached by their short arms 46,X,i dic(X) (p223::p223) A 45,X cell line was present in 40% of cultured lymphocytes but only in 2% of fibroblasts cultured from the right gonad and absent in fibroblasts from the left gonad and skin. The abnormal chromosome had one Cd-positive, active centromere and one inactive centromere. A study of DNA replication with autoradiography and BrdU treatment revealed that the abnormal X was always the late replicating one. In a proportion of cells there was an asymmetric pattern of replication : the region with the inactive centromere had a tendency to replicate later than the portion with the functioning centromere. The Xg blood group segregation suggested that the attached X chromosomes were of paternal origin and therefore a true isodicentric formed after an isochromatid break followed by joining of the two sister chromatids.