Categories: Skeleton phene (incl. short stature & teeth) , Reproductive system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614839 (trait) , 162330 (gene)

Single-gene trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: Testicular Hypoplasia and Persistent Primary Dentition

Molecular basis: Whole-genome sequencing of a Domestic Shorthair cat with delayed puberty, and subsequent searching for private variants in 40 comparative candidate genes for the homologous trait (hypogonadotropic hypogonadism) in humans enabled Hug et al. (2019) to identify a potentially causal variant as "TAC3:c.220G>A or p.(Val74Met)". The authors noted that TAC3 encodes "tachykinin 3, a precursor protein of the signaling molecule neurokinin B, which is known to play a role in sexual development". The authors stressed the need for caution with this result: "Given that this is a single case investigation and that we have no functional confirmation of neurokinin B deficiency, this result must be considered preliminary and should be interpreted with caution."

Clinical features: Hug et al. (2019): "A 3-year-old male domestic shorthair cat was presented with persistent primary dentition consisting of one primary maxillary canine . . . . Upon examination there was one small right testicle located in the scrotum. The left testicle could not be located. It was neither scrotal, nor palpable in the inguinal area. The external genitalia, including the urethral orifice, were in the normal position, although with a juvenile appearance because of their small size. The hair coat had an unkempt appearance. The cat had small body size but proportional growth. It had reportedly displayed mounting behavior toward another female cat in the household and showed an increasingly dominant–aggressive behavior toward other cats outside. The cat was presented for a follow-up examination at 4 years of age. No changes in behavior or the stage of adolescence were noticed."

Prevalence: Hug et al. (2019): "The affected cat was homozygous for the mutant allele. In a cohort of 171 randomly sampled cats, 169 were homozygous for the wildtype allele and 2 were heterozygous."

Control: Interestingly, Hug et al. (2019) noted that "In felines, efforts are underway to develop a method to permanently sterilize cats by RNAi-mediated silencing of KISS1 and TAC3 [KISS1 is another gene which, when mutated, gives rise to Hypogonadotropic hypogonadism in humans]. This method is predicted to lead to a reduction in the stray animal population and therefore decrease animal suffering and vectors for human disease".

Breed: Domestic Shorthair (Cat) (VBO_0100119).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: