OMIA 002162-9615 : Hypophosphatasia in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 241500

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific symbol: HPP

History: The paper by Kyöstilä et al. (2019) is another example of the first report of a disorder that also presents a likely causal variant for that disorder.

Molecular basis: Kyöstilä et al. (2019): "Exome sequencing of one affected dog revealed a homozygous missense variant (c.1301T > G; p.V434G) in the tissue non-specific alkaline phosphatase gene, ALPL."

Clinical features: Kyöstilä et al. (2019): "The disease was recognized in seven KBD puppies with a variable presentation of skeletal hypomineralization, growth retardation, seizures and movement difficulties"

Pathology: Kyöstilä et al. (2019): "Overall, the pathological findings in affected dogs were compatible with a generalized skeletal ossification and mineralization defect. The specific finding of C cell hyperplasia was indicative of long-term hypercalcemia and compatible with the elevated serum calcium level measured in one affected puppy."

Prevalence: Kyöstilä et al. (2019): "The identified recessive variant showed full segregation with the disease in a cohort of 509 KBDs with a carrier frequency of 0.17 and was absent from 303 dogs from control breeds."

Breed: Karelian bear dog.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ALPL alkaline phosphatase, liver/bone/kidney Canis lupus familiaris 2 NC_006584.3 (77614102..77559791) ALPL Homologene, Ensembl, NCBI gene

Variants

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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Karelian bear dog Hypophosphatasia ALPL missense CanFam 3.1 2 g.77561953A>C c.1301T>G p.V434G 2019 30700765

Reference


2019 Kyöstilä, K., Syrjä, P., Lappalainen, A.K., Arumilli, M., Hundi, S., Karkamo, V., Viitmaa, R., Hytönen, M.K., Lohi, H. :
A homozygous missense variant in the alkaline phosphatase gene ALPL is associated with a severe form of canine hypophosphatasia. Sci Rep 9:973, 2019. Pubmed reference: 30700765. DOI: 10.1038/s41598-018-37801-2.

Edit History


  • Created by Frank Nicholas on 01 Feb 2019
  • Created by Frank Nicholas on 04 Feb 2019
  • Changed by Frank Nicholas on 04 Feb 2019