In other species: dog

Categories: Endocrine / exocrine gland phene (incl mammary gland)

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 202010 (trait) , 610613 (gene)

Links to MONDO diseases:

• MONDO:0008729: congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: This is a type of XX difference of sexual development (DSD) due to variants in the CYP11B1 gene.

Species-specific name: Congenital adrenal hypoplasia (CAH)

Species-specific symbol: CAH

Inheritance: Knighton (2004) reported a single cat with deficiency of 11-beta hydroxylase. Since the deficiency is due to a mutation in the gene that encodes this enzyme (see below), the disorder is almost certainly autosomal recessive.

Molecular basis: Adopting the comparative candidate-gene strategy (based on the similarity of diagnostic signs of a single affected cat with the homologous human disorder), Owens et al. (2012) sequenced the feline CYP11B1 gene (encoding 11β-hydroxylase) in that single affected cat and a healthy control cat, identifying the causal mutation as a G>A missense SNP in exon 7 "that results in an arginine to glutamine amino acid substitution; this latter mutation results in 11β-hydroxylase deficiency-associated CAH in people".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Key clinical features reflect the deficiency of the enzyme (11β-hydroxylase) and consequential impaired biosynthesis of cortisol and changes to androgen levels (Owens et al., 2012; Stachowiak, 2022), including presence of indeterminant or secondary sex characteristics post desexing, including gynecomastia (enlarged breast tissue) concurrent with fully formed penis with barbs (Knighton, 2004; Owens et al., 2012); intermale aggression (Owens et al., 2012); unexplained hypertension and excess salt and water retention (Owens et al., 2012); polyuria and polydipsia (Knighton, 2004; Owens et al., 2012); foul-smelling and minimally concentrated urine (Owens et al., 2012); small body frame, thickened skin and greasy haircoat (Owens et al., 2012); decreased baseline and stimulated serum cortisol and aldosterone concentrations (Owens et al., 2012); increased baseline and stimulated progesterone and androstenedione concentrations (Owens et al., 2012) and increased serum urea nitrogen concentration, hypernatremia, hyperglobulinemia (Owens et al., 2012).

IT thanks DVM student Angela Jeppesen, who provided the basis of this contribution in May 2023.

Breeds: Domestic medium-haired, Domestic Shorthair.
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: