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

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 173110 (gene) , 613038 (trait)

Links to relevant human diseases in MONDO:

• MONDO:0024464: pituitary hormone deficiency, combined, 1

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific name: combined pituitary hormone deficiency dwarfism; hypopituitarism dwarfism

Species-specific description: see also OMIA 000307-9615: Dwarfism, pituitary, generic and OMIA 002314-9615 : Dwarfism, pituitary, LHX3-related in Canis lupus familiaris

Mapping: Kyöstilä et al. (2021) "obtained samples from five [Karelian bear dogs] KBDs presenting dwarfism and abnormal coats. A combined analysis of genome-wide association and next-generation sequencing mapped the disease to a region in chromosome 31 ... ."

Molecular basis: Kyöstilä et al. (2021) "identified a homozygous intronic variant in the fourth exon of the POU1F1 gene in the affected dogs. The identified variant, c.605-3C>A, resided in the splice region and was predicted to affect splicing. The variant’s screening in three new prospective cases, related breeds, and ~ 8000 dogs from 207 breeds indicated complete segregation in KBDs with a carrier frequency of 8%, and high breed-specificity as car-riers were found at a low frequency only in Lapponian Herders, a related breed."

Clinical features: Karelian bear dogs with the homozygous POU1F1 defect present with proportional dwarfism, being approximately 18cm smaller in height than unaffected KBDs (Andresen & Willeberg, 1976). Affected dogs either retain their puppy coat or appear to have a regular adult coat until around 2-3 years of age when their hair coat is almost completely lost (Andresen & Willeberg, 1976). Clinical presentations can be more severe with early onset neurological signs including seizures and blindness in puppies (Kyostila et al., 2021). IT thanks DVM student Gemma Campbell, who provided the basis of this contribution in May 2023

Breeds: Karelian Bear Dog (Dog) (VBO_0200754), obsolete Carelian Beardogs (Dog) (VBO_0200292).
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: