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 organization: Department of Medical and Clinical Genetics
STEMM - Stem Cells and Metabolism Research Program
Veterinary Biosciences
University of Helsinki
Research Programs Unit
Research Programme for Molecular Neurology
Veterinary Pathology and Parasitology
Antti Sukura / Principal Investigator
Departments of Faculty of Veterinary Medicine
Equine and Small Animal Medicine
Hannes Tapani Lohi / Principal Investigator
Medicum
Genome-Scale Biology (GSB) Research Program
Faculty of Veterinary Medicine
Veterinary Genetics
Helsinki One Health (HOH)
Petbone – ortopedia, fysioterapia, kivunlievitys
Date: 2019-01-30
Language: eng
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-018-37801-2
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
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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