Cytogenetic and molecular characterization of two isodicentric Y chromosomes

Abstract

We report the results of detailed molecular-cytogenetic studies of two isodicentric Y [idic(Y)] chromosomes identified in patients with complex mosaic karyotypes. We used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) to determine the structure and genetic content of the abnormal chromosomes. In the first patient, classical cytogenetics and FISH analysis with Y chromosome-specific probes showed in peripheral blood lymphocytes a karyotype with 4 cell lines: 45,X[128]/46,X,+idic(Y)(p11.32)[65]/47,XY,+idic(Y)(p11.32)[2]/47,X,+2idic(Y)(p11.32)[1]. No Y chromosome material was found in the removed gonads. For precise characterization of the Yp breakpoint, FISH and fiberFISH analysis, using a telomeric probe and a panel of cosmid probes from the pseudoautosomal region PAR1, was performed. The results showed that the breakpoint maps approximately 1,000 Kb from Ypter. The second idic(Y) chromosome was found in a boy with mild mental retardation, craniofacial anomalies, and the karyotype in lymphocytes 47,X,+idic(Y)(q11.23),+i(Y)(p10)[77]/46,X,+i(Y)(p10)[23]. To our knowledge, such an association has not been previously described. FISH and PCR analysis indicated the presence of at least two copies of the SRY gene in all analyzed cells. Using 17 PCR primers, the Yq breakpoint was shown to map between sY123 (DYS214) and sY121 (DYS212) loci in interval 5O in AZFb region. Possible mechanisms of formation of abnormal Y chromosomes and karyotype-phenotype correlations are discussed.

Dynamic mosaicism manifesting as loss, gain and rearrangement of an isodicentric Y chromosome in a male child with growth retardation and abnormal external genitalia

“…Since the idic(Y)(q11.23) cell line is more common and monocentric Y chromosomes are reported to be more stable than dicentric ones (Haaf and Schmid, 1990), 'initial' chromosome aberration is probably idic(Y)(q11.23), whereas i(Y)(p10) seems to be produced through the rearrangement of idic(Y)(q11.23). Taking into account previous reports (Haaf and Schmid, 1990;Stankiewicz et al, 2001;Codina-Pascual et al, 2004;DesGroseilliers et al, 2006;Liehr et al, 2007), one can suggest that instability of idic(Y)(q11.23) is the main reason for its loss and gain. Together this is evidence for post-zygotic origin of all cell lines apart from idic(Y)(q11.23) and suggests that the index case represents an example of dynamic mosaicism.…”

“…Likewise, cases exhibiting further rearrangements of an isodicentric Y chromosome are uncommon (DesGroseilliers et al, 2006). There is a report of a boy with i(Y)(p10) and idic(Yq11.23) suggesting related karyotypes produce the male phenotype, but 45,X cells were not observed in that case (Stankiewicz et al, 2001). Tissue-specific distribution proposed as a mechanism of sex determination seems to be the closest explanation of phenotype in the index case.…”

“…Mosaicism is commonly observed in cases of rearranged Y chromosomes (Hsu, 1994;Stankiewicz et al, 2001;Codina-Pascual et al, 2004;DesGroseilliers et al, 2006). Recently, Liehr et al (2007) have shown that the majority of cases of marker chromosomes derived from the Y chromosome are 45,X/46,X,der(Y) mosaics.…”

“…Rearranged Y chromosome gain is considerably more rarely reported than 45,X/46,X,idic(Y) conditions. However, there is a strong correlation between the number of metaphase spreads scored and occurrence of chromosome gains in such cases (Stankiewicz et al, 2001;Codina-Pascual et al, 2004). Thus, probably, this cell line was frequently overlooked.…”

“…More precise evaluations of such cases by fluorescence in situ hybridization (FISH) have evidenced that mosaicism mediated by loss or gain of the rearranged Y chromosome could be dynamic, i.e. changing during ontogeny (Stankiewicz et al, 2001;Codina-Pascual et al, 2004;DesGroseilliers et al, 2006). Consequently, analysis of similar cases provides new clues on mitotic mosaicism formation at least in cases of structurally rearranged chromosome loss.…”