Molecular breakpoint analysis and relevance of variable mosaicism in a woman with short stature, primary amenorrhea, unilateral gonadoblastoma, and a 46,X,del(Y)(q11)/45,X karyotype

Abstract

We report on a 30-year-old woman with short stature, completely female external genitalia, primary amenorrhea, bilateral streak gonads, unilateral gonadoblastoma, and a 46,X,del(Y)(q11)/45,X karyotype. Variable levels of mosaicism were found in blood and cultivated fibroblasts from both the skin and ovaries, with the percentage of the 45,X lineage never exceeding 33%. Fluorescence in situ hybridization (FISH) was performed with alpha satellite centromere region probes of the X and Y chromosomes (DXZ1 and DXZ3) as well as with the unique-sequence, locus-specific, sex-determining region of the Y chromosome gene (SRY) and the DXZ1 probes. Each signal was noted for DXZ1 on the X chromosome and for the Y probes on the marker chromosome. Molecular investigations with a panel of PCR markers spread over the whole Y chromosome indicated a deletion breakpoint between sY 78 (interval 4) and sY 151 (interval 5F). No mutation of the high mobility group-box (HMG-box) of the SRY gene could be found following sequence analysis. The phenotype/genotype correlation demonstrates the broad phenotypic range of low-level 45,X mosaicism with the resultant short stature and external female phenotype, despite the presence of SRY in a high proportion of cells in various tissues.

Prenatal diagnosis of sex chromosome mosaicism with two marker chromosomes in three cell lines and a review of the literature

“…The SNP microarray analysis performed on the DNA extracted from amniotic fluid revealed two Y chromosomes and 7.8-Mb deletions involving the region in Yq11.222q12. The molecular karyotype was arr[hg19] (X)x1, (Y)x2, Yq11.222q12 (21,032,786,812)x0 ( Fig. 2A and B).…”

“…Phenotypes associated with the two sex chromosomal mosaicism vary from females with Turner syndrome to males with infertility, and include individuals with ambiguous genitalia (1). Their phenotypic spectrums are very broad and variable, and are attributed to variable locations of the breakpoints and to the proportion of 45,X cells distributed over the different tissues (9,21,22).…”

Molecular and clinical description of a girl with a 46,X,t(Y;4)(q11.2;p16)/45,X,der(4)t(Y;4)(q11.2;p16) karyotype and a small cryptic 4p subtelomeric deletion

“…When the structural rearrangement involves a Y chromosome, the resulting phenotype depends on the complexity of the rearrangement, the presence or absence of Y-specific loci, such as SRY, stature or spermatogenesis-promoting genes, and, in case of mosaicism, the proportion of the different cell lines [Daniel, 1985;Kelly et al, 1998;Reddy and Sulcova, 1998;Morava et al, 2000;Stankiewicz et al, 2001;Kotzot et al, 2002;Alvarez-Nava et al, 2003]. The disorders associated with such abnormalities include male dysgenetic pseudohermaphroditism, mixed gonadal dysgenesis, and Turner syndrome with an associated risk of gonadoblastoma.…”

Molecular and cytogenetic characterization of a non‐mosaic isodicentric Y chromosome in a patient with Klinefelter syndrome

“…If the breakpoints in the idicY chromosome occur in the short arms of the Y chromosome and the SRY gene is deleted, a female phenotype can be expected. If the SRY region is spared, a male phenotype or due to mosaicism a female with Turner‐like features and intra‐abdominal gonads can result [Genuardi et al, 1995; Udler et al, 2001; Kotzot et al, 2002].…”