Prenatal and postnatal characterization of Y chromosome structural anomalies by molecular cytogenetic analysis

Abstract

We describe three cases in which we used fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) and comparative genomic hybridization (CGH) to characterize Y chromosome structural anomalies, unidentifiable by conventional G-banding. Case 1 was a 46,X,+mar karyotype; FISH analysis revealed an entire marker chromosome highlighted after hybridization with the Y chromosome painting probe. The PCR study showed the presence of Y chromosome markers AMG and SY620 and the absence of SY143, SY254 and SY147. CGH results confirmed the loss of Yq11.2-qter. These results indicated the presence of a deletion: del(Y)(q11.2). Case 2 was a 45,X [14]/46,XY[86] karyotype with a very small Y chromosome. The PCR study showed the presence of Y chromosome markers SY620 and AMG, and the absence of SY143, SY254 and SY147. CGH results showed gain of Yq11.2-pter and loss of Yq11.2-q12. These results show the presence of a Yp isodicentric: idic(Y)(q11.2). Case 3 was a 45,X,inv(9)(p11q12)[30]/46,X,idic(Y)(p11.3?),inv(9)(p11q12)[70] karyotype. The FISH signal covered all the abnormal Y chromosome using a Y chromosome paint. The PCR study showed the presence of Y chromosome markers AMG, SY620, SY143, SY254 and SY147. CGH only showed gain of Yq11.2-qter. These results support the presence of an unbalanced (Y;Y) translocation. Our results show that the combined use of molecular and classical cytogenetic methods in clinical diagnosis may allow a better delineation of the chromosome regions implicated in specific clinical disorders.

Patient with a non‐mosaic isodicentric Yp and mild developmental delay

“…There have been a number of previously reported cases of isodicentric Yp [Gaal et al, 1978; Hsu, 1994; Genuardi et al, 1995; Robinson et al, 1999; Hernardo et al, 2002; Yoshitsugu et al, 2003]. However, almost all cases to date have been mosaic cases, with the second cell line typically being 45,X.…”

Mixed gonadal dysgenesis in a child with isodicentric y chromosome: Does the relative proportion of the 45,X line really matter?

“…In fact, most patients with idic(Y) are mosaic for an additional cell line, mostly 45,X [Robinson et al, 1999]. There is phenotypic variability among patients with 45,X/46,X, idic(Y) mosaicism [Hernando et al, 2002; DesGroseilliers et al, 2006] which was attributed to variable location of the breakpoints and to the proportion of 45,X cells distributed over the different tissues [Alvarez‐Nava et al, 2003; DesGroseilliers et al, 2006]. Idic(Y) causes a wide range of sex‐linked reproductive disorders, including spermatogenic failure, sex reversal, mixed gonadal dysgenesis, and Turner syndrome; accordingly the patients may have normal male external genitalia, ambiguous genitalia, or normal female genitalia [Hsu, 1994].…”

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

“…The routine G-band staining analysis indicated that the fetus had a mosaic karyotype with two marker chromosomes in three cell lines. The abnormal karyotype was 45,X [13]/46,X,+mar1 [6]/46,X,+mar2 [9], and the mosaic proportion was 46, 21 and 33% (13/28, 6/28 and 9/28 cells), respectively ( Fig. 1A-C).…”

“…A dicentric Y chromosome is a common abnormal structural rearrangement between sister chromatids and is unstable during cell division; therefore, it is highly likely to generate various cell lines, including 45,X and delY cell lines. Previous studies have mostly described individuals with ambiguous genitalia and mixed gonadal dysgenesis who were diagnosed with sex chromosome mosaicism postnatally (1,(8)(9)(10)(11)(12)(13)(14)(15)(16). However, there are few studies reporting prenatally diagnosed fetuses, particularly with three different cell lines.…”