Prenatal diagnosis of the maternal derivative chromosome der(15)t(Y;15)(q12;p13) in a dizygotic twin pregnancy

Abstract

Sex chromosome translocations are unique and must be considered separately from translocations between autosomes. Here, we describe the first prenatal case of one twin fetus with an unbalanced translocation between chromosome Y and chromosome 15, presenting a 46,XY,der(15)t(Y;15) karyotype. The other twin had a normal 46,XY karyotype. Cytogenetic analysis of the parental chromosomes revealed that the father had a normal 46,XY karyotype, whereas the mother exhibited a 46,XX,der(15) t(Y;15) karyotype. Thus, the proband inherited this translocation from the mother. Fluorescence in situ hybridization analyses demonstrated that the breakpoint on chromosome Y involved a heterochromatin region (Yq12), while that on chromosome 15 involved a p-arm region (15p13). At 37 gestational weeks, healthy twins were delivered vaginally. We conclude that accurate identification of der(15) chromosomal content can facilitate not only prenatal diagnosis of a chromosomal aberration in one twin, but also prediction of the fetal phenotype.

Keywords: Prenatal diagnosis; Sex chromosome aberrations; Twin pregnancy.

Fig. 1

Cytogenetic characterization of the der(15) translocation. (A) Pedigree data for the family. The father (I-1) has a normal karyotype, and the mother (I-2) is the der(15) translocation carrier. The arrow represents the proband II-1, who harbors the same translocation as his mother. His twin brother II-2 has a normal karyotype. (B) GTG-banded partial karyotypes show chromosome 15 in the family compared with the pedigree; the arrows indicate that the proband and his mother carry additional material on the p-arm of chromosome 15. (C) CTG-banded partial karyotypes show that both the proband (II-1) and his mother (I-2) exhibit dark staining on the p-arm of chromosome 15, mainly indicating a heterochromatic content.

Fig. 2

FISH characterization of the breakpoints between chromosome 15 and chromosome Y. Commercially available alpha-DNA satellite probes for the X and Y chromosomes (DXZ1 and DYZ3), a centromere 15 probe (D15Z4), an acro p-arm probe (acro-p), and a Y-specific probe (DYZ1) were used. (A) FISH analysis was carried out on metaphase spreads from amniotic fluid cells. All acrocentric chromosomes including chromosomes #13, #14, #15, #21, and #22 were stained red on the p-arm by an acro-p probe. The arrow shows that the der(15) chromosome from the proband contains the chromosome 15 centromere (D15Z4/green +), but exhibits loss of 15p (acro-p/red –), indicating that the original translocation breakpoint on chromosome 15 was in the p-arm. (B) Analysis of the proband's cells using the Y chromosome-specific probes DYZ1 and DYZ3 revealed that the Y chromosome is normal, indicated by an arrowhead (DYZ1/aqua + and DYZ3/red +). The der(15) chromosome contains the chromosome 15 centromere and Yq12 heterochromatic region, but not the Yp11.1-q11.1 region, indicated by an arrow (D15Z4/green +, DYZ1/aqua +, and DYZ3/red –). (C,D) FISH analysis was carried out on the blood lymphocytes of the proband's mother. D15Z4, DYZ1, and DYZ3 probes were used. The arrow indicates that her der(15) chromosome contains the chromosome 15 centromere and Yq12 heterochromatic region, but not the Yp11.1-q11.1 region (D15Z4/green +, DYZ1/aqua +, and DYZ3/red –), results similar to those of the proband. With the X chromosome-specific probe DXZ1, FISH results show a normal female with two X chromosomes (DXZ1/red +). FISH = fluorescence in situ hybridization.

Fig. 3

Ideograms for the der(15) structural rearrangement. Ideograms of a normal chromosome 15, Y chromosome, and the derivative chromosome 15; the breakpoints are indicated with black arrows.