Pituitary Dwarfism, LHX3 related

 

Gene: LHX3

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.

Mutations:

German Shepherd, Czechoslovakian Wolfdog, Tibetan Terrier mutation: Deletion, LHX3 gene: deletion 7 bp from a microsatellite repeat in intron 5-6

German Shepherd mutation: Insertion, LHX3 gene; c.545_547 duplication, p.(N182 duplication)

Medical systems: Skeletal, endocrine

Breeds: Czechoslovakian Wolfdog, German Shepherd, Saarloos Wolfhound, Tibetan Terrier

Age of onset of symptoms: 2-3 months

Pituitary dwarfism is a disease caused by a defect in the differentiation of endocrine cells of the pituitary gland.  Under normal conditions, these cells secrete somatotropin (growth) hormone which is necessary for normal growth and development.  Without this hormone, the affected dog has delayed growth and development and the appearance of a well-proportioned dwarf.  Numerous systems are affected.  The skin becomes darker, there is retention of puppy hair and eventually total loss of hair.  The eruption of permanent teeth is delayed.  The functioning of the thyroid, adrenals and gonads is altered.  Affected dogs can have mental retardation, immune system deficiencies and a reduced life expectancy.

 

References:

OMIA link: [0307-9615], [2314-9615]

Kitzmann S, Hartmann K, Zablotski Y, et al. (2021) Wellbeing, quality of life, presence of concurrent diseases, and survival times in untreated and treated German Shepherd dogs with dwarfism. PLoS One 16:e0255678.  [pubmed/34370756]

Kyöstilä K, Niskanen JE, Arumilli M, et al. (2021) Intronic variant in POU1F1 associated with canine pituitary dwarfism. Hum Genet. 140(11):1553-1562. [pubmed/33550451]

Thaiwong T, Corner S, Forge S, Kiupel M. (2021) Dwarfism in Tibetan Terrier dogs with an LHX3 mutation. J Vet Diagn Invest 33:740-3. [pubmed/33890524]

Voorbij AM, Meij BP, van Bruggen LW, et al. (2015) Atlanto-axial malformation and instability in dogs with pituitary dwarfism due to an LHX3 mutation.  J Vet Intern Med. 29(1):207-13. [pubmed/25586673]

Voorbij AM, Leegwater PA, Kooistra HS. (2014) Pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs is associated with a mutation in LHX3.  J Vet Intern Med. 28(6):1770-1774. [pubmed/25273400]

Voorbij AM, van Steenbeek FG, Vos-Loohuis M et al. (2011) A contracted DNA repeat in LHX3 intron 5 is associated with aberrant splicing and pituitary dwarfism in German Shepherd dogs.  Plos ONE 6(11):e27940. [pubmed/22132174]