Molecular Genetic Characterization of Thyroid Dyshormonogenesis in a French Bulldog

Journal of Veterinary Internal Medicine

S. Major²  R.W. Pettigrew¹ 

[1] Southern California Veterinary Specialty Hospital, Irvine, CA;Rancho Regional Veterinary Hospital, Rancho Cucamonga, CA

关键词: Goiter;    Inborn error;    Mutation;    RNA splicing;    Thyroid peroxidase;   

DOI  :  10.1111/jvim.13651

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC   
Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

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