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.
Highlights
Neocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location
To 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
Extensive analysis of neocentromere formation has led to the conclusion that neocentromere activation occurs via an unknown epigenetic mechanism that, in effect, converts a previously non-centromeric genetic locus into a functional neocentromere that associates with all of the proteins involved in active centromere function [6]
Summary
Neocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location. Neocentromeres are rare human chromosomal aberrations that have apparently formed within interstitial chromosomal sites that have not previously been known to express centromere function. Extensive analysis of neocentromere formation has led to the conclusion that neocentromere activation occurs via an unknown epigenetic mechanism that, in effect, converts a previously non-centromeric genetic locus into a functional neocentromere that associates with all of the proteins involved in active centromere function [6]. This process has recently been described as neocentromerization [7]
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