Verification of a cryptic t(Y;15) translocation in a male with an apparent 45,X karyotype

Abstract

Background: A rare disease is that an individual with a non-chimeric karyotype of 45,X develops into a male. We explored the genetic aetiology of an infertile male with an apparent 45,X karyotype, which was subsequently verified as cryptic translocation between chromosomes Y and 15.

Methods: DNA was extracted from the patient's peripheral blood. A range of genetic testing was performed, including conventional chromosomal karyotyping, short tandem repeat (STR) analysis for azoospermia factor (AZF) region, fluorescence in situ hybridization (FISH) with specific probes groups of DXZ1/DYZ3, DYZ3/D15Z1/PML and SRY/D15Z1/PML, and chromosomal microarray analysis (CMA) for genomic copy number variations (CNVs).

Results: The patient was found to have an apparent 45,X karyotype. STR analysis showed that he possessed a short arm of the Y chromosome, including the SRY gene; however, he was missing the long arm of the Y chromosome, including AZFa + b + c and Yqter. A FISH assay of DXZ1 and DYZ3 probes showed a green signal of the X centromere and a red of the Y centromeric signal on a D-group-sized chromosome. By FISH assaying with D15Z1 and DYZ3 probes, chromosomes 15 and Y centromeric signals appeared closely on a single chromosome, as the PML control probe ascertained. A further FISH assay with D15Z1 and SRY probes revealed a signal of the SRY gene at the end of one arm of chromosome 15. The result of the CMA indicated a deletion with an approximate size of 45.31 Mb spanning from Yq11 to Yter.

Conclusion: Our study enriched the karyotype-phenotype correlation of Y and 15 chromosomes translocation. It strengthened the critical roles of molecular genetic techniques in identifying the chromosomal breakpoints and regions involved. Genetic aetiology can guide early intervention in childhood and assisted reproduction in adulthood.

Keywords: 45,X male; Azoospermia factor; Chromosomal microarray analysis; Fluorescence in situ hybridization; Sex-determining region Y gene; Y chromosome translocation.

Fig. 1

a: Karyogram of the t(Y;15) male patient. The der(15) and X chromosomes are indicated by arrows. b: Ideograms of chromosomes Y, 15, and dic(Y;15). The Y centromere and 15 centromere of the dicentric chromosome are indicated by arrows. c: 46,XY karyogram of the patient's father. d: 46,XX karyogram of the patient's mother

Fig. 1

a: Karyogram of the t(Y;15) male patient. The der(15) and X chromosomes are indicated by arrows. b: Ideograms of chromosomes Y, 15, and dic(Y;15). The Y centromere and 15 centromere of the dicentric chromosome are indicated by arrows. c: 46,XY karyogram of the patient's father. d: 46,XX karyogram of the patient's mother

Fig. 2

Capillary electrophoresis diagram for the detection of AZF sequences. a: Normal male; b: Normal female; c: 45,X male. A fluorescence peak representing the SRY sequence was seen, but those for the AZFa, AZFb, AZFc, and SY160 were absent, suggesting loss of the whole long arm of the Y chromosome

Fig. 3

a: FISH image of metaphase cells of the patient detected with the X and Y centromeric probes. The green signal indicated the centromere of the X chromosome, while the red signal indicated the Y chromosome material on a D-group-telocentromeric chromosome; b: FISH image of metaphase cells of the patient's father detected with the 18, X and Y centromeric probes. The blue, green, red signals are indicated the 18, X, Y chromosomes

Fig. 4

FISH image of metaphase cells of the patient detected with centromeric probes for chromosomes 15 and Y. The green signal is from the PML probe mapped to 15q24.1, the red signal is from the DYZ3 probe mapped to the centromere of Y, and the aqua blue signal is from the D15Z1 probe (15q10) closely located on the same chromosome

Fig. 5

FISH image of metaphase cells of the patient detected with probes for chromosome 15 and the SRY region. The green signal is from the PML probe mapped to 15q24.1, the orange signal from the SRY probe (Yp11.31) and the aqua blue signal from the D15Z1 probe (15q10) are located on the same chromosome

Fig. 6

CMA result of the patient. The Yq region was absent in the patient. The red bar indicates the area of deletion