Neocentric X-chromosome in a girl with Turner-like syndrome
- Equal contributors
1 Cytogenetics Dept, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA
2 Deparment of Genetics and Genomic Sciences, Mount Sinai School of Medicine, NY, USA
3 Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92690, USA
Molecular Cytogenetics 2012, 5:29 doi:10.1186/1755-8166-5-29Published: 9 June 2012
Neocentromeres 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.
G-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)/45,X, 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.
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.