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Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog
BACKGROUND: A case of congenital hypothyroidism with goiter (CHG) in a juvenile French bulldog was identified and hypothesized to be caused by dyshormonogenesis of genetic etiology. OBJECTIVES: To describe case management, unusual phenotypic aspects, and a CHG‐causing mutation in a French bulldog. A...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895686/ https://www.ncbi.nlm.nih.gov/pubmed/26478542 http://dx.doi.org/10.1111/jvim.13651 |
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author | Major, S. Pettigrew, R.W. Fyfe, J.C. |
author_facet | Major, S. Pettigrew, R.W. Fyfe, J.C. |
author_sort | Major, S. |
collection | PubMed |
description | BACKGROUND: A case of congenital hypothyroidism with goiter (CHG) in a juvenile French bulldog was identified and hypothesized to be caused by dyshormonogenesis of genetic etiology. OBJECTIVES: To describe case management, unusual phenotypic aspects, and a CHG‐causing mutation in a French bulldog. ANIMALS: Thyroid tissue and blood from a CHG‐affected French bulldog and 4 normal control dogs and buccal brush samples of 125 French bulldogs were studied. METHODS: Standard clinical assessment and laboratory tests were applied. Thyroid peroxidase (TPO) iodide oxidation activity was measured in vitro, and TPO protein was assessed on Western blots. Thyroid peroxidase exons and flanking splice sites were amplified from genomic DNA and sequenced. Thyroid peroxidase cDNA was amplified from thyroid RNA and sequenced. RESULTS: At 9 months of age, the affected dog had signs of cretinism, but near‐normal skeletal maturation. The enlarged thyroid glands exhibited noninflammatory fibrosis and aberrant follicular organization. Thyroid peroxidase activity and immunocrossreactive protein were undetectable. There was a T>C mutation of the intron 12 splice donor consensus that caused abnormally spliced mRNA, consistent with absent TPO function. The mutant allele was not observed in 125 clinically normal French bulldogs. CONCLUSIONS: Presumptive CHG in a French bulldog with unusual clinical presentation is described. Genetic etiology was confirmed by identifying the underlying TPO mutation. |
format | Online Article Text |
id | pubmed-4895686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48956862016-06-22 Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog Major, S. Pettigrew, R.W. Fyfe, J.C. J Vet Intern Med SMALL ANIMAL BACKGROUND: A case of congenital hypothyroidism with goiter (CHG) in a juvenile French bulldog was identified and hypothesized to be caused by dyshormonogenesis of genetic etiology. OBJECTIVES: To describe case management, unusual phenotypic aspects, and a CHG‐causing mutation in a French bulldog. ANIMALS: Thyroid tissue and blood from a CHG‐affected French bulldog and 4 normal control dogs and buccal brush samples of 125 French bulldogs were studied. METHODS: Standard clinical assessment and laboratory tests were applied. Thyroid peroxidase (TPO) iodide oxidation activity was measured in vitro, and TPO protein was assessed on Western blots. Thyroid peroxidase exons and flanking splice sites were amplified from genomic DNA and sequenced. Thyroid peroxidase cDNA was amplified from thyroid RNA and sequenced. RESULTS: At 9 months of age, the affected dog had signs of cretinism, but near‐normal skeletal maturation. The enlarged thyroid glands exhibited noninflammatory fibrosis and aberrant follicular organization. Thyroid peroxidase activity and immunocrossreactive protein were undetectable. There was a T>C mutation of the intron 12 splice donor consensus that caused abnormally spliced mRNA, consistent with absent TPO function. The mutant allele was not observed in 125 clinically normal French bulldogs. CONCLUSIONS: Presumptive CHG in a French bulldog with unusual clinical presentation is described. Genetic etiology was confirmed by identifying the underlying TPO mutation. John Wiley and Sons Inc. 2015-10-18 2015 /pmc/articles/PMC4895686/ /pubmed/26478542 http://dx.doi.org/10.1111/jvim.13651 Text en Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | SMALL ANIMAL Major, S. Pettigrew, R.W. Fyfe, J.C. Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog |
title | Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog |
title_full | Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog |
title_fullStr | Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog |
title_full_unstemmed | Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog |
title_short | Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog |
title_sort | molecular genetic characterization of thyroid dyshormonogenesis in a french bulldog |
topic | SMALL ANIMAL |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895686/ https://www.ncbi.nlm.nih.gov/pubmed/26478542 http://dx.doi.org/10.1111/jvim.13651 |
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