Class II neocentromeres: a putative common neocentromere site in band 4q21.2

Neocentromeres are rare functional centromeres formed within noncentromeric chromosomal regions. We report the finding of a neocentromere in a very rare class II analphoid chromosome. This neocentromere was detected prenatally in a fetus with the karyotype: 47,XY,del(4)(p15.3q21.1),+r(4)(p15.3q21.1).ish del(4)(D4S3360+,WHS+,D4Z1-,4qsubtel+),r(4)(D4S3360-,WHS-,D4Z1+,4qsubtel-)de novo. The fetus was missing one normal chromosome 4 but had a ring chromosome, consisting of the pericentromeric region of chromosome 4, and a deleted chromosome 4, the reciprocal product of the ring formation. In situ hybridization established that the chromosome 4 pericentromeric heterochromatin was located on the ring chromosome, while the Wolf-Hirschhorn critical region and chromosome 4 subtelomeric regions were present on the deleted chromosome. A C-band-negative constriction was observed in band 4q21.2 of the deleted chromosome 4, indicating that a neocentromere had been formed in this band, allowing stable segregation during cell division. This chromosome abnormality was detected in cultured amniocytes from a 20-week pregnancy presenting with intrauterine growth retardation and echogenic bowel. The pregnancy resulted in intrauterine death at 33-34 weeks. Despite the apparently balanced karyotype, the fetus is likely to have been phenotypically impaired due to disruption of genes by the neocentromere, rearrangement and ring chromosome formation. There has been one previous report of neocentromere formation in band 4q21; the observation presented here might refine a putative common neocentromeric site to sub-band 4q21.2.