In other species: Burton's mouthbrooder , dog , horse , pig , taurine cattle

Categories: Reproductive system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 300068 (trait) , 313700 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0019154: androgen insensitivity syndrome

Mendelian trait/disorder: yes

Mode of inheritance: X-linked

Disease-related: yes

Key variant known: no

Cross-species summary: This is a type of XY difference of sexual development (XY DSD) due to variants in the AR gene. Previously known as Testicular Feminisation Syndrome. This is an abnormality of sexual development in which affected individuals have an XY chromosomal constitution, undescended testes and female secondary sexual characteristics (including female external genitalia). Also, instead of normally developed Mullerian duct derivatives (Fallopian tubes, uterus, cervix, and upper protion of the vagina), they have under-developed Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle). In all species so far investigated, the inheritance is X-linked recessive. In several species, this disorder is known to be due to a deficiency of an androgen receptor encoded by a gene on the X chromosome. The presence of a Y chromosome induces the undifferentiated embryonic gonads to develop as testes, but, in the absence of androgen receptor, the androgens produced by the testes cannot exert any effect. The result is that the embryo follows the "default" path of development, which is female.

Species-specific description: Testicular feminization syndrome is a type of XY Disorder of Sexual Development (DSD) in which the androgen receptor is nonfunctional, causing complete androgen insensitivity syndrome (CAIS). Affected cats have a normal male karyotype (38,XY) and develop testes, but develop into phenotypic females that are sterile. It is an X-linked trait. Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Inheritance: As the AR is located on the X chromosome, XY males having one copy of the mutant AR are affected. Female carriers are heterozygous.

Mapping: FCX

Clinical features: Affected cats appear to be phenotypically normal females, but fail to exhibit estrous cycles at the age of puberty (primary anesrus). Affected cats have a male karyotype (38,XY) and undescended testes, but no other male or female reproductive organs are found internally (Meyers-Wallen et al., 1989).

Pathology: As the androgen receptor is nonfunctional, the testosterone signaling pathway is interrupted, which causes complete failure of androgen-dependent masculinization in the internal and external genitalia. Affected cats lack epididymides and vasa deferentia and develop labia, a clitoris and a blind-ending caudal vagina. As the testes produce Müllerian inhibiting substance as expected, the Müllerian duct system regresses normally, causing absence of the oviducts, uterus, and cranial vagina (Meyers-Wallen et al., 1989).

Prevalence: Rare

Control: Further breeding of the dam of the affected cat is not recommended.

Genetic testing: Cats can be tested for a qualitative or quantitative defect in the androgen receptor by testing androgen binding in genital fibroblasts (Meyers-Wallen et al., 1989).

Breed: Domestic Shorthair.
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).