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Dr. Fyfe and MSU announce DNA-based carrier test for deadly Congenital Hypothyroidism with Goiter in newborn puppies, kittens, goats, and lambs. PART 2 of 3.

 

 

CHG 3: Congenital Hypothyroidism with Goiter (CHG)

John C. Fyfe, D.V.M., Ph.D. Part 3 of 4 part exclusive interview by TheDogPlace.org

2019 Update by Barbara J. Andrews

 

Congenital Hypothyroidism With Goiter is a "thyroid problem" but unlike idiopathic, dietary, or environmentally induced thyroid hormone imbalance, there is little that dog breeders can do other than never repeat a breeding that produced CHG and test any related dogs before breeding.

 

The information below is provided by Dr. Fyfe who is no longer with Michigan State University but is associated with a research company. As a breeder and student of real-life genetics, I urge you to form your own opinion regarding the necessity of testing for CHG. If any dog in your breeding program has ever produced CHG it would be wise to test that dog.

 

We also stipulate that while this congenital thyroid gland defect occurs in the Toy Fox Terrier, it is not limited to that breed nor to the canine species. It also occurs in cats, goats, and other animals.  If you missed Part 1 About Congenital Hypothyroidism With Goiter you should read that first. Also explore the Display Links below but be sure to come back here for Part 3 on Cost and Testing for CHG.

 

Genetic Basis and Cause for CHG

 

Dr. John C. Fyfe - In a cooperative effort of breeders, veterinarians, and a canine genetics researcher at the Michigan State University College of Veterinary Medicine, the genetic basis of congenital hypothyroidism with goiter (CHG) in Toy Fox Terriers (TFT) has been discovered, and a DNA-based carrier test is now available. Thyroid hormone is essential for normal development and metabolism in dogs, especially in the rapid growth period that puppies experience. Pups affected with CHG are abnormal from just a few days of age. They do not move around as much as normal pups, and the head may appear large in comparison to the body. Most have died or were euthanized by 3 weeks of age. If nursing care is given and they survive as long as 3 weeks, the eyes do not open, the ear canals remain very small, and the hair coat is abnormally bristly. By the second week of age, a swelling on the underside of the neck can be felt and continues to enlarge with time. The swelling may be mistaken for lymph nodes in making an incorrect diagnosis of puppy strangles. Delay in lengthening of bones in the legs, spine, and face causes dwarfism. Most all abnormalities are alleviated by early diagnosis and daily oral administration of thyroid hormone medication, but this does not stop the goiter from continuing to enlarge and constricting the airway. Even treated, this is a disfiguring disorder. Many TFT breeders have been aware for years that pups as described above have been born occasionally, but until recently few have received a correct diagnosis or indication that the disorder was inherited. Affected puppies have occurred in breeding programs across the United States of America and in New Zealand.

 

Before you speculate, the case(s) referenced in other veterinary sources has never been confirmed. CHG has however been confirmed in other breeds and even other species including cats.

 

Recent studies have demonstrated that the disorder is inherited as a simple autosomal recessive trait. For a puppy to have CHG, it must received the mutated copy (allele) of the disease gene from both parents, and male and female puppies are equally affected. The parents of affected pups show no outward signs of disease, but they are obligate carriers, by definition. In a breeding program, both male and female carriers will pass on their mutant alleles to 50% of all their offspring, on average. When two carriers are inadvertently mated, on average 25% of the puppies will have CHG. That means that in litters from such matings, there may be some combination of CHG and normal pups, all CHG puppies, or all normal puppies. Unidentified carriers in breeding programs continue to spread the mutant allele throughout the TFT breed.

 

CHG in TFT is caused by lack of thyroid peroxidase (TPO), an enzyme in the thyroid gland responsible for adding iodine to a protein called thyroglobulin. A mutation in the TPO gene prevents production of the enzyme and the consequent inability to produce thyroid hormones. Identification of the TPO mutation has allowed design of a laboratory test to detect the mutation in DNA from dog blood, cheek cells, and frozen semen. DNA isolated from samples is subjected to a polymerase chain reaction (PCR) to amplify the portion of the TPO gene harboring the mutation. Normal and mutant alleles are differentiated by their susceptibility to cutting with a molecular scissors called a restriction enzyme. Thus, in a DNA sample from a genetically normal TFT all of the PCR product cuts, but in a carrier only the half of the product amplified from the normal allele cuts. Therefore, carrier dogs can be positively identified in the laboratory on the basis of the presence of the mutant allele in their DNA.

 

This test is offered to TFT breeders through the Laboratory of Comparative Medical Genetics at Michigan State University in hopes that it will be used to eliminate CHG from TFT breeding programs. Testing results are given only to the person submitting the dog’s sample and are kept strictly confidential. For instructions on submitting samples, please point your internet browser to http://www.msu.edu/unit/mic/facpages/fyfeform.asp or contact Dr. John C. Fyfe by email: fyfe@cvm.msu.edu or at the address below.

 

After May 20, 2002 our address will be:

Laboratory of Comparative Medical Genetics

2209 Biomedical Physical Sciences

Michigan State University

East Lansing, MI 48824

 

We are trying to determine If any study data was released to the Toy Fox Terrier Club or to OFA.  If you KNOW of a Toy Fox Terrier litter that contained congenital hypothyroidism with goiter (CHG) we ask you to email the editor.  If you request anonymity, we will respect your wishes.  The numerical results of this new 2019 survey will be reported here and to the Toy Fox Terrier Club Of America. If you own another breed or know of a breed club that keeps CHG records, again, please email me and we will contact them.

 

We ask all breeders to contact us to report a confirmed occurrence of GHG in any breed or species for our privacy protected veterinary database.

 

For more information on other breeds (and species) affected by Congenital Hypothyroidism with Goiter, see Part 1 - CHG Introduction.

 

Part 2 - About Congenital Hypothyroidism with Goiter (CHG)     Part 4 - CHG-4 Testing Cost, by Dr. Fyfe

Copyright TheDogPlace.org 124g1411R191 http://www.thedogplace.org/GENETICS/CHG-3-Congenital-Hypothyroidism-genetic-basis-Fyfe-DVM.asp

 

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