Parental origin of the X chromosome, X chromosome mosaicism and screening for “hidden” Y chromosome in 45,X Turner syndrome ascertained cytogenetically

Abstract

Our study confirms the finding that about 85% of X chromosomes in Turner girls are maternally derived. A new observation is the detection of a high frequency of mosaicism (15%) in Turner girls who by cytogenetic analysis were thought to have a pure 45,X karyotype. DNA examination of the material was done by hybridization with digoxigenin labelled, non‐radioactive probes, and PCR products for microsatellite analysis were run on polyacrylamide gels. We screened for the presence of “hidden” Y chromosome mosaicism, using the primers SRY, ZFY, DYZ3, DYZ1 and DYS132. Contrary to other reports using the PCR technique to unravel “hidden” Y chromosome mosaics, we did not find any positive cases. A precise technical protocol for these new techniques is given, and the advantages are discussed.

Detection of Y Chromosomal Material in Patients with a 45,X Karyotype by PCR Method

“…However, the frequency of Y sequences in patients with TS varies from 0% to 61% depending on the molecular methods used and the patient population studied. This variability may be caused by the number of the patients with mosaic marker chromosome, selection of the Y chromosome specific primers, different tissues tested and molecular methodology used by different study groups (Kokova et al 1993;Binder et al 1995;Coto et al 1995;Larsen et al 1995;Patsalis et al 1997;Osipova et al 1998;Lopez et al 1998;Quilter et al 1998;Mendes et al 1999;Fernandez-Garcia et al 2000;Gravholt et al 2000;Nishi et al 2002;Alvarez-Nava et al 2003). Therefore, it is difficult to compare our results with previously reported results.…”

“…In the view of their findings, they concluded that nested PCR could have overestimated the results. Binder et al (1995), Coto et al (1995), Larsen et al (1995), Fernandez et al (1996 and Lopez et al (1998) used similar Y specific sequences and found that the ratio of Y sequences in patients with a 45,X karyotype were 3.3%, 26.6%, 9.1%, 11.1%, 12%, respectively. Quilter et al (1998) reported 4% (2/50) in patient have a 45,X karyotype with eight primer set along Y chromosome.…”

Cryptic mosaicism involving a second chromosome X in patients with Turner syndrome

“…The frequency reported varies from 0-75% (Table 2) (1,3,11,(15)(16)(17)(18)(19)(20)(21)(22)(23) and in most cases a second X chromosome was detected, but skewed inactivation is not. Although peripheral blood may not represent the rest of the tissues of the body, analysis of samples of other tissues usually depends on invasive procedures.…”

“…This has led to the widely held hypothesis that, in order to be viable, a 45,X conceptus must possess another cell line, at least in some critical organs or at a critical period during embryogenesis (1,2). For this reason, many females with TS stigmata who have been ascribed a non-mosaic 45,X karyotype after cytogenetic analysis of a limited number of cells may, in fact, be mosaics (3). In addition to occult mosaicism, other factors affecting the phenotype have not yet been fully elucidated, including genomic imprinting or anomalous X inactivation, leading to difficulties in diagnosis and genetic counseling (4).…”

Turner syndrome: counseling prior to oocyte donation

“…The introduction of molecular biology techniques such as the polymerase chain reaction (PCR) has revealed the existence of hidden mosaics not detected by cytogenetic examination, ranging in frequency from 0% to 61% according to the techniques used. 3,4 The presence of Y chromosome material in individuals with the TS stigmata and gonadal dysgenesis is associated with the development of gonadoblastoma, a tumor containing nests of germ cells and cells resembling Sertoli or granulosa cells. 5 The risk has been previously estimated to be up to 30%.…”