Neocentric X-chromosome in a girl with Turner-like syndrome

Abstract

BackgroundNeocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location. We report the finding of a structurally abnormal X chromosome with a neocentromere in a 15-year-old girl with clinical features suggestive of Turner syndrome, including short stature and primary amenorrhea.ResultG-banded chromosome analysis revealed a mosaic female karyotype involving two abnormal cell lines. One cell line (84% of analyzed metaphases) had a structurally abnormal X chromosome (duplication of the long arm and deletion of the short arm) and a normal X chromosome. The other cell line (16% of cells) exhibited monosomy X. C-banding studies were negative for the abnormal X chromosome. FISH analysis revealed lack of hybridization of the abnormal X chromosome with both the X centromere-specific probe and the “all human centromeres” probe, a pattern consistent with lack of the X chromosome endogenous centromere. A FISH study using an XIST gene probe revealed the presence of two XIST genes, one on each long arm of the iso(Xq), required for inactivation of the abnormal X chromosome. R-banding also demonstrated inactivation of the abnormal X chromosome. An assay for centromeric protein C (CENP-C) was positive on both the normal and the abnormal X chromosomes. The position of CENP-C in the abnormal X chromosome defined a neocentromere, which explains its mitotic stability. The karyotype is thus designated as 46,X,neo(X)(qter- > q12::q12- > q21.2- > neo- > q21.2- > qter)[42]/45,X[8], which is consistent with stigmata of Turner syndrome. The mother of this patient has a normal karyotype; however, the father was not available for study.ConclusionTo our knowledge, this is the first case of mosaic Turner syndrome involving an analphoid iso(Xq) chromosome with a proven neocentromere among 90 previously described cases with a proven neocentromere.

A Turner Syndrome Patient Carrying a Mosaic Distal X Chromosome Marker

“…This represents a much smaller duplication than our case study and was also nonmosaic but is another example of functional disomy of a part of the X chromosome. Hemmat et al [ 10 ] described a rare case of an acentric marker X chromosome containing an activated neocentromere distal to this case study, at Xq21.2. This example raises the possibility of a similar sequence (of DNA with a degree of homology to centromeric sequences) being present in the marker of the case described here, which has been forced into activation to give it stability in cell division.…”

A complete duplication of X chromosome resulting in a tricentric isochromosome originated by centromere repositioning

“…In literature, Hemmat et al [ 13 ] described a neocentric X-chromosome in a girl showing Turner-like syndrome, but the neocentromere was analphoid and no signals were detected after FISH with X-centromere specific probe or all human centromeres. The i(Xq) was constituted of two q arms and only two partial p arms differently from case here presented.…”