The first case of 38,XX (SRY-positive) disorder of sex development in a cat

Abstract

Background: SRY-positive XX testicular disorder of sex development (DSD) caused by X;Y translocations was not yet reported in domestic animals. In humans it is rarely diagnosed and a majority of clinical features resemble those which are typical for Klinefelter syndrome (KS). Here we describe the first case of SRY-positive XX DSD in a tortoiseshell cat with a rudimentary penis and a lack of scrotum.

Results: Molecular analysis showed the presence of two Y-linked genes (SRY and ZFY) and a normal sequence of the SRY gene. Application of classical cytogenetic techniques revealed two X chromosomes (38,XX), but further FISH studies with the use of the whole X chromosome painting probe and BAC probes specific to the Yp chromosome facilitated identification of Xp;Yp translocation. The SRY gene was localised at a distal position of Xp. The karyotype of the studied case was described as: 38,XX.ish der(X)t(X;Y)(p22;p12)(SRY+). Moreover, the X inactivation status assessed by a sequential R-banding and FISH with the SRY-specific probe showed a random inactivation of the derivative X(SRY) chromosome.

Conclusions: Our study showed that among DSD tortoiseshell cats, apart from XXY trisomy and XX/XY chimerism, also SRY-positive XX cases may occur. It is hypothesized that the extremely rare occurrence of this abnormality in domestic animals, when compared with humans, may be associated with a different organisation of the Yp arm in these species.

Keywords: Cat; DSD; Disorder of sex development; Intersexuality; SRY; Translocation X-Y; X chromosome inactivation.

Figure 1

Phenotype of the cat: A) external genitalia, B) underdeveloped penis, C) identification of ductus deferens during surgery, D) histology of the ductus deferens.

Figure 2

Molecular detection of SRY and ZFX/ZFY genes. A) The presence of the SRY gene amplicon in leukocytes and fibroblasts of the cat. SRY positive and SRY negative controls were included in the analysis, B) ZFX and ZFY genes were detected both in leukocytes and fibroblasts. ZFX/ZFY and ZFX/ZFX controls were included in the analysis.

Figure 3

Cytogenetic analysis. A) Schematic presentation of the feline Yp arm, based on Li et al. [10], and location of the used BAC clones B) Dual-colour FISH with the use of whole X chromosome painting probe (red) and SRY-specific BAC probe (green).

Figure 4

Inactivation status of X and X ^SRY chromosomes. A) and C) R-banded metaphases, B) and D) FISH with SRY -specific BAC probe (red) on the same DAPI-banded metaphases. Active X chromosome is marked by a solid circle and inactive by a doted circle.