Campus Units

Veterinary Clinical Sciences, Biomedical Sciences

Document Type

Article

Publication Version

Published Version

Publication Date

4-16-2020

Journal or Book Title

Scientific Reports

Volume

10

First Page

6558

DOI

10.1038/s41598-020-63451-4

Abstract

Mucopolysaccharidosis (MPS) is a metabolic storage disorder caused by the deficiency of any lysosomal enzyme required for the breakdown of glycosaminoglycans. A 15-month-old Boston Terrier presented with clinical signs consistent with lysosomal storage disease including corneal opacities, multifocal central nervous system disease and progressively worsening clinical course. Diagnosis was confirmed at necropsy based on histopathologic evaluation of multiple organs demonstrating accumulation of mucopolysaccharides. Whole genome sequencing was used to uncover a frame-shift insertion affecting the alpha-L-iduronidase (IDUA) gene (c.19_20insCGGCCCCC), a mutation confirmed in another Boston Terrier presented 2 years later with a similar clinical picture. Both dogs were homozygous for the IDUA mutation and shared coat colors not recognized as normal for the breed by the American Kennel Club. In contrast, the mutation was not detected in 120 unrelated Boston Terriers as well as 202 dogs from other breeds. Recent inbreeding to select for recessive and unusual coat colors may have concentrated this relatively rare allele in the breed. The identification of the variant enables ante-mortem diagnosis of similar cases and selective breeding to avoid the spread of this disease in the breed. Boston Terriers carrying this variant represent a promising model for MPS I with neurological abnormalities in humans.

Comments

This article is published as Mansour, Tamer A., Kevin D. Woolard, Karen L. Vernau, Devin M. Ancona, Sara M. Thomasy, Lionel Sebbag, Bret A. Moore et al. "Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog." Scientific Reports 10 (2020): 6558. DOI: 10.1038/s41598-020-63451-4. Posted with permission.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Copyright Owner

The Author(s)

Language

en

File Format

application/pdf

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