A homozygous missense variant in the alkaline phosphatase gene ALPL is associated with a severe form of canine hypophosphatasia

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Kyöstilä , K , Syrjä , P , Lappalainen , A K , Arumilli , M , Hundi , S , Karkamo , V , Viitmaa , R , Hytönen , M K & Lohi , H 2019 , ' A homozygous missense variant in the alkaline phosphatase gene ALPL is associated with a severe form of canine hypophosphatasia ' , Scientific Reports , vol. 9 , 973 . https://doi.org/10.1038/s41598-018-37801-2

Title: A homozygous missense variant in the alkaline phosphatase gene ALPL is associated with a severe form of canine hypophosphatasia
Author: Kyöstilä, Kaisa; Syrjä, Pernilla; Lappalainen, Anu K.; Arumilli, Meharji; Hundi, Sruthi; Karkamo, Veera; Viitmaa, Ranno; Hytönen, Marjo K.; Lohi, Hannes
Contributor: University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Veterinary Pathology and Parasitology
University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Equine and Small Animal Medicine
University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Hannes Tapani Lohi / Principal Investigator
Date: 2019-01-30
Language: eng
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/300016
Abstract: Inherited skeletal disorders affect both humans and animals. In the current study, we have performed series of clinical, pathological and genetic examinations to characterize a previously unreported skeletal disease in the Karelian Bear Dog (KBD) breed. The disease was recognized in seven KBD puppies with a variable presentation of skeletal hypomineralization, growth retardation, seizures and movement difficulties. 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. 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. In humans, recessive and dominant ALPL mutations cause hypophosphatasia (HPP), a metabolic bone disease with highly heterogeneous clinical manifestations, ranging from lethal perinatal hypomineralization to a relatively mild dental disease. Our study reports the first naturally occurring HPP in animals, resembling the human infantile form. The canine HPP model may serve as a preclinical model while a genetic test will assist in breeding programs.
Subject: PYRIDOXINE-RESPONSIVE SEIZURES
INFANTILE HYPOPHOSPHATASIA
MATRIX VESICLES
PERINATAL HYPOPHOSPHATASIA
MUTATION
BONE
VITAMIN-B6
NOSOLOGY
GENOTYPE
PYRIDOXAL-5'-PHOSPHATE
413 Veterinary science
1184 Genetics, developmental biology, physiology
3111 Biomedicine
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