Clinical, cytogenetic, and molecular findings of isodicentric Y chromosomes

Abstract

BackgroundIsodicentric Y chromosomes [idic(Y)] are one of the most common structural abnormalities of the Y chromosome. The prenatal diagnosis of isodicentric Y chromosomes is of vital importance, and the postnatal phenotypes vary widely. Therefore, we present six patients prenatally diagnosed with isodicentric Y chromosomes and review the literature concerning the genotype-phenotype correlations.MethodThe clinical materials of six patients were obtained. Cytogenetic and molecular approaches were carried out for these six patients.ResultsIsodicentric Y chromosomes were found in all sixpatients. Among them, four patients presented with a mosaic 45,X karyotype, one patient had a 46,XY cell line, and one patient was nonmosaic. Five of these six isodicentric Y chromosomes had a breakpoint in Yq11.2, and the other had a breakpoint in Yp11.3. The molecular analysis demonstrated different duplications and deletions of the Y chromosome. Finally, three patients chose to terminate the pregnancy, two patients gave birth to normal-appearing males, and one patient was lost to follow-up.ConclusionThe incorporation of multiple cytogenetic and molecular techniques would offer a more comprehensive understanding of this structural chromosomal abnormality for genetic counselling.

Canary in the Coal Mine? Male Infertility as a Marker of Overall Health

“…Other abnormalities of the Y chromosome include isodicentric Y chromosomes. These occur from chromosomal translocation or chromatid fusion after a Y chromosomal break and result in two centromeres and associated gene duplications or loss (166). Depending on the region of the Y chromosome that is gained or lost, variable phenotypic presentations and mosaicism result, including short stature (in up to 80% of cases), ambiguous genitalia (in up to 75% of cases), language delay, autism, learning difficulties, growth delay, dysmorphic features, and mental disorders (25,34).…”

Optical genome mapping for detection of chromosomal aberrations in prenatal diagnosis

“…Generally, a combination of CMA and karyotyping are needed for prenatal diagnosis of isodicentric Y-chromosomes, as the phenotypes depend on the breakage and fusion of the isodicentric Y-chromosomes and the types and proportions of mosaicism. [30][31][32][33][34][35][36] In case 34, the breakpoints detected by the CNV and SV algorithms were consistent with CMA. The SV algorithm determined the chromosome rearrangement mode of the dual centromeres, and the mosaic state suggested by the CNV algorithm was also consistent with the karyotyping.…”

“…Isodicentric Y‐chromosomes are commonly found in Y‐chromosome structural aberrations in prenatal diagnosis. Generally, a combination of CMA and karyotyping are needed for prenatal diagnosis of isodicentric Y‐chromosomes, as the phenotypes depend on the breakage and fusion of the isodicentric Y‐chromosomes and the types and proportions of mosaicism 30–36 . In case 34, the breakpoints detected by the CNV and SV algorithms were consistent with CMA.…”

Male infertility and genitourinary birth defects: there is more than meets the eye

“…As an extension to this, given the variable function of genes on the Y chromosome, abnormal fusion or translocation of the Y chromosome may result in additional phenotypes found in a subset of Y chromosome-microdeleted men. Isodicentric Y chromosomes represent one such change, and this results in a Y chromosome with two centromeres with associated gene duplication and/or loss depending on the regions involved (58). Therefore, numerous mosaic and phenotypic patterns may be seen in those with Y chromosome-associated conditions (i.e., microdeletions or CNVs of PAR1/PAR2 genes), including ambiguous genitalia (up to 75%), short stature, autism, language delay, dysmorphic facial features, mental disorders, and growth delay (59).…”