Symmetric replication of an unstable isodicentric Xq chromosome derived from isolocal maternal sister chromatid recombination

Abstract

An amniocyte culture was found to be mosaic for 45,X/46,X, idic(X)(p11.2)/ 47,X, idic(X)(p11.2),idic(X)(p11.2) cell lines, reflecting mitotic nondisjunction of the idic(X)(p11.2) chromosome. Upon learning of abnormal karyotype and ultrasound findings, the parents decided to discontinue the pregnancy. Subsequent cultures of fetal skin, kidney, and lung were mosaic 45,X/46,X,idic(X)(p11.2) reflecting mitotic loss of the unstable idic(X)(p11.2) chromosome. C-banding and in situ hybridization of X chromosome-specific alpha-satellite probe to metaphase fetal cells confirmed two centromeres on the idic(X)(p11.2) chromosome with both centromeres appearing to be active in two-thirds of cells. This result was confirmed by centromere protein-E (CENP-E) antibody staining which delineated 80% of scored cells with two active centromeres and 20% with 1 active centromere. Bromodeoxyuridine (BrdU) incorporation and acridine orange staining characterized the DNA replication pattern of the idic(X)(p11.2) chromosome as late and symmetrically replicating. Polymerase chain reaction analysis of highly polymorphic loci determined that the normal X chromosome carried paternal alleles and the idic(X)(p11.2) chromosome carried maternal alleles from only one grandparental chromosome. Overall, the results suggest that recombination occurred between two maternal sister chromatids both in the same chromosome band Xp11.2 (isolocal) prior to maternal meiosis II anaphase to generate an unstable maternal idic(X)(p11.2) chromosome. Additional factors that could contribute to i(Xq) and idic(X) formation and instability are discussed along with a mechanism to explain the high frequency of intrauterine loss in 45,X pregnancies.

Large inverted repeats within Xp11.2 are present at the breakpoints of isodicentric X chromosomes in Turner syndrome

“…In addition, idic(X)(p11) chromosomes have not been reported with a 46,X,idic(X)(p11)/46,XX mosaic karyotype, indicating they are meiotically derived, and no parent of origin bias has been observed (14)(15)(16)(17). Mosaicism with a 46,X,idic(X)(p11)/ 45,X karyotype is present in 40% of cases (18), suggesting that the two active centromeres of the idic(X)(p11) chromosome may be mitotically unstable, resulting in anaphase lag and breakage (19). Moreover, previous studies using a-CENP-C and a-CENP-E staining as markers of active centromeres indicated that functionally monocentric idic(X)(p11) chromosomes segregated normally in mitosis, whereas those that were functionally dicentric had a tendency toward anaphase lag (20).…”

Case report of a pseudo‐isodicentric chromosome 9 resulting in mosaic trisomy 9

“…13 In the second scenario, during G 1 phase of the cell cycle, a small terminal deletion is followed by a U-shaped rejoining of the broken chromatids, or "sticky" chromatids, after the replication of the deleted portion, that forms the isochromosome. 14 Due to the mosaic nature of the abnormality seen in this patient, the isochromosome likely arose from a mitotic error which has been proposed for other mosaic autosomal isochromosomes. 15 However, the exact mechanism resulting in isochromosome formation in this patient is unknown.…”

“…The first process takes place during either the S or the G 2 phase of the cell cycle in either mitosis or meiosis, where a break occurs in both chromatids followed by rejoining of the broken ends (referred to as an isolocal U‐shaped sister chromatid exchange) resulting in an isodicentric chromosome 13 . In the second scenario, during G 1 phase of the cell cycle, a small terminal deletion is followed by a U‐shaped rejoining of the broken chromatids, or “sticky” chromatids, after the replication of the deleted portion, that forms the isochromosome 14 . Due to the mosaic nature of the abnormality seen in this patient, the isochromosome likely arose from a mitotic error which has been proposed for other mosaic autosomal isochromosomes 15 .…”

Prenatal diagnosis and molecular cytogenetic analysis of a de novo isodicentric chromosome 18

“…One is an isolocal U-shape sister chromatid exchange (isolocal break in two chromatids and rejoining of broken ends) in either the S or G2 phase 3. The other is a chromosomal deletion during the G1 phase and U-shape rejoining of the broken ends of the chromatid after replication of the deleted chromosome 4. Both mechanisms will result in a symmetrical isodicentric chromosome.…”