Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene
Background A congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss. Hypothesis/Objectives The...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-03-01
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| Series: | Journal of Veterinary Internal Medicine |
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| Online Access: | https://doi.org/10.1111/jvim.15060 |
| _version_ | 1818308791443128320 |
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| author | Julien Guevar Natasha J. Olby Kathryn M. Meurs Oriana Yost Steven G. Friedenberg |
| author_facet | Julien Guevar Natasha J. Olby Kathryn M. Meurs Oriana Yost Steven G. Friedenberg |
| author_sort | Julien Guevar |
| collection | DOAJ |
| description | Background A congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss. Hypothesis/Objectives The objectives of this study were to use whole genome sequencing (WGS) to identify deleterious genetic variants in candidate genes associated with the syndrome and to study the prevalence of candidate variants among a population of unaffected Doberman Pinschers. Animals One affected Doberman Pinscher and 202 unaffected Doberman Pinschers. Methods WGS of the affected dog with filtering of variants against a database of 154 unaffected dogs of diverse breeds was performed. Confirmation of candidate variants was achieved by Sanger sequencing followed by genotyping of the control population of unaffected Doberman Pinschers. Results WGS and variant filtering identified an alteration in a gene associated with both deafness and vestibular disease in humans: protein tyrosine phosphatase, receptor type Q (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a frameshift mutation in exon 39 of the gene. This insertion is predicted to cause a protein truncation with a premature stop codon occurring after position 2054 of the protein sequence that causes 279 C‐terminal amino acids to be eliminated. Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous for the reference allele. Conclusion and Clinical Importance We report the identification of a genetic alteration on the PTPRQ gene that is associated with congenital hearing and vestibular disorder in a young Doberman Pinscher dog. |
| first_indexed | 2024-12-13T07:19:53Z |
| format | Article |
| id | doaj.art-518b90ab284d4cdeb8c252d4732c918e |
| institution | Directory Open Access Journal |
| issn | 0891-6640 1939-1676 |
| language | English |
| last_indexed | 2024-12-13T07:19:53Z |
| publishDate | 2018-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj.art-518b90ab284d4cdeb8c252d4732c918e2022-12-21T23:55:26ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762018-03-0132266566910.1111/jvim.15060Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ geneJulien Guevar0Natasha J. Olby1Kathryn M. Meurs2Oriana Yost3Steven G. Friedenberg4School of Veterinary Medicine, University of WisconsinMadison WisconsinCollege of Veterinary Medicine, North Carolina State UniversityRaleigh North CarolinaCollege of Veterinary Medicine, North Carolina State UniversityRaleigh North CarolinaCollege of Veterinary Medicine, North Carolina State UniversityRaleigh North CarolinaCollege of Veterinary Medicine, University of MinnesotaSaint Paul MinnesotaBackground A congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss. Hypothesis/Objectives The objectives of this study were to use whole genome sequencing (WGS) to identify deleterious genetic variants in candidate genes associated with the syndrome and to study the prevalence of candidate variants among a population of unaffected Doberman Pinschers. Animals One affected Doberman Pinscher and 202 unaffected Doberman Pinschers. Methods WGS of the affected dog with filtering of variants against a database of 154 unaffected dogs of diverse breeds was performed. Confirmation of candidate variants was achieved by Sanger sequencing followed by genotyping of the control population of unaffected Doberman Pinschers. Results WGS and variant filtering identified an alteration in a gene associated with both deafness and vestibular disease in humans: protein tyrosine phosphatase, receptor type Q (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a frameshift mutation in exon 39 of the gene. This insertion is predicted to cause a protein truncation with a premature stop codon occurring after position 2054 of the protein sequence that causes 279 C‐terminal amino acids to be eliminated. Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous for the reference allele. Conclusion and Clinical Importance We report the identification of a genetic alteration on the PTPRQ gene that is associated with congenital hearing and vestibular disorder in a young Doberman Pinscher dog.https://doi.org/10.1111/jvim.15060deafnessDoberman PinschergeneticsPTPRQvestibular disease |
| spellingShingle | Julien Guevar Natasha J. Olby Kathryn M. Meurs Oriana Yost Steven G. Friedenberg Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene Journal of Veterinary Internal Medicine deafness Doberman Pinscher genetics PTPRQ vestibular disease |
| title | Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene |
| title_full | Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene |
| title_fullStr | Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene |
| title_full_unstemmed | Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene |
| title_short | Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene |
| title_sort | deafness and vestibular dysfunction in a doberman pinscher puppy associated with a mutation in the ptprq gene |
| topic | deafness Doberman Pinscher genetics PTPRQ vestibular disease |
| url | https://doi.org/10.1111/jvim.15060 |
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