Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog.
- Resource Type
- Academic Journal
- Authors
- Mansour TA; Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, United States. drtamermansour@gmail.com.; Department of Clinical Pathology, School of Medicine, Mansoura University, Mansoura, Egypt. drtamermansour@gmail.com.; Woolard KD; Department of Pathology, Immunology and Microbiology, School of Veterinary Medicine, University of California, Davis, CA, United States.; Vernau KL; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, United States.; Ancona DM; VCA West Coast Specialty and Emergency Animal Hospital, Fountain Valley, CA, United States.; Thomasy SM; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, United States.; Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, CA, United States.; Sebbag L; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.; Moore BA; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, United States.; Knipe MF; William R Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA, United States.; Seada HA; Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States.; Cowan TM; Department of Pathology, Stanford University, Palo Alto, CA, United States.; Aguilar M; Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, United States.; Titus Brown C; Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, United States.; Bannasch DL; Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, United States. dlbannasch@ucdavis.edu.
- Source
- Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
- Subject
- Language
- English
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.