There is great discrepancy between phenotype-karyo­type in individuals having a chromosomal mosaicism involving one single line 45,X, or two or more lines with structural abnormalities of the Y chromosome. In Case 1, 10% of cells contained isodicentric Y chromosome derived from the long arm. In Case 2, the mosaic karyotype showed elevated number of cells (35%) bearing an abnormal Y derived from the short arm of the Y chromosome. Irrespective of the size and shape of the two isodicentrics, both cases were SRY-positive on FISH analysis. All methods used for characterization of the derivative Y chromosome clearly demonstrated that in our cases, both the percentage of cells bearing isochromosomes and breakpoint location in isodicentrics were completely different.

      In Case 1, the breakpoint in the derivative Yq chromosome was placed distally from the subtelomeric locus DXYS130 in Yp. We must emphasize that this patient harbors a significant population of 45,X cells (90%), while the cells with 46,X,idic(Y)(p11.3) constitute 10%. Previously reported results showed that the percentage of cells with dicentric Yq chromosome was markedly higher being more stable than the Yp dicentric [14].

      The question that arises from our results is: why was an isodicentric composed of almost the entire Y chromosome not able to sustain a normal male phenotype? We speculate that very soon after fertilization, both centro­meres of the isodicentric Y chromosome were functional. Loss of this chromosome through failure of correct mitotic segregation and anaphase lag, produced increasing amounts of the 45,X clone. These results suggest a novel mechanism for the formation of the 45,X Turner syn­drome, and highlight an important potential risk for generation of phenotypic anomalies frequently associated with sex chromosome mosaicism, including ambiguous genitalia [20].

      In Case 2 the 46,X,idic(Y)(q11) cells constituted 35% with a fusion point proximal to the DYS392 locus in the euchromatic region q11. Thus, the position of the q arm breakpoint in the isodicentric Yp chromosome did not seem to influence stability of derivative Y, as had been proposed on the hypothesis that the more proximal the location of the breakpoint on the Yq arm, the less stable the dicentric Yp chromosomes and hence higher numbers of 45,X cells [13,15].

      The cell lines containing the dicentric Yp chromosome with the breakpoint proximal on the q arm were more prevalent (35%) than in Case 1, in which fewer cells contained idic(Y)(p11.3) (10%) and the breakpoint was situated distally from the subtelomeric locus DXYS130 in Yp. We agree therefore, that “multiple areas of Y specific repeat sequences along the Y chromosome q arm are susceptible to breakage and reunion and in these cases formation of dicentrics” [21].

      We have demonstrated in two patients with ambiguous genitalia and features of Turner syndrome different numbers of cells bearing isodicentrics of Y chromosome in peripheral blood lymphocytes. Fluorescence in situ hybridization and PCR allowed a precise evaluation of the mosa­icism and using molecular markers, characterization of the chromosomal breakpoints in derivative Y chromosomes. Despite their difference in shape and size, the two derivative Y chromosomes retained the SRY gene, which seems to be the common element of ambiguous genitalia phenotype.           

      Reporting of these rare chromosomal abnormalities is important to increase our knowledge of genotype-phenotype correlations and add valuable information when associated with a comprehensive review of the literature. Our results confirm the necessity for cytogenetic investigation of each patient with an abnormal gender phenotype. The undesirable consequence of chromosome Y structural abnormalities on a carrier’s phenotype highlights the importance of sex chromosome integrity for normal gender phenotype development. Shape and size differences of a Y chromosome may distort the gender determination pathway.