Pituitary Dwarfism, POU1F1 related

Gene: POU1F1

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, POU1F1 gene; c.605-3 C>A

Medical systems: Skeletal, endocrine

Breeds: Karelian Bear Dog

Age of onset of symptoms: Several weeks after birth.

Pituitary dwarfism is an autosomal recessive genetic condition reported in several dog breeds, notably the German Shepherd and the Karelian Bear Dog breeds.  The anterior pituitary is an endocrine gland containing several cell types that are responsible for the production and secretion of a number of hormones including growth hormone (somatotrophin) and thyroid-stimulating hormone.  Genetic disruptions in the development of the anterior pituitary or in the expression of specific hormone genes can result in growth disturbances described as pituitary dwarfism.  In the German Shepherd breed, a proportional dwarfism with reduced height and weight and including alopecia is described.  This is caused by a mutation in the LHX3 gene which codes for a transcription factor that is needed for normal pituitary development.  In a small cohort of Dutch German Shepherd dogs, a carrier frequency for the LHX3 mutation was measured at 18.9%.  In the Karelian Bear Dog breed, a proportional dwarfism is seen that can also include alopecia.  This time the genetic defect is in the POU1F1 gene, which codes for a transcription factor needed for somatotroph cell differentiation and for growth hormone gene expression.  A carrier frequency of 8% was measured for the POU1F1 mutation within the Karelian Bear Dog breed in Finland.

Genetic tests for these mutations can now be used by breeders to identify carrier animals to make appropriate breeding decisions to eliminate the condition and eventually eliminate the mutation from the breed.

References:

OMIA link: [2315-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Kyöstilä K, Niskanen JE, Arumilli M, et al. (2021) Intronic variant in POU1F1 associated with canine pituitary dwarfism. Hum Genet 140:1553-62.  [pubmed/33550451]

Andresen E, Willeberg P. (1977) Pituitary dwarfism in Carelian bear-dogs: evidence of simple, autosomal recessive inheritance. Hereditas 84:232-4.  [pubmed/838602]

Contributed by:  Shao Doyon-Degroote and Maude Robin, Class of 2028, Faculty of Veterinary Medicine, University of Montreal.  (Translation, DWS)