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Fanconi Syndrome Basenji Type (FS)
| Acronym: | FS |
| Gene: | FAN1 |
| Mutation: | g.38013703del317bp |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Fanconi Syndrome Basenji type is a genetic disorder caused by proximal renal tubular dysfunction. Fanconi syndrome was named after swiss doctor Guido Fanconi, who was the first to describe the disorder in 1936. Canine Fanconi syndrome was first reported in 1976 in the Basenji dog breed. FS can be divided into hereditary and idiopathic (the cause is not known). Idiopathic FS has been identified in the Norwegian Elkhound, Labrador Retriever, Shetland Sheepdog, and Miniature Schnauzer. Forms of FS that are acquired as a result of the toxic effects of certain drugs or heavy metal poisoning are also common. In Fanconi syndrome, proximal renal tubular epithelial cells are insufficient, which leads to urinary leakage, or insufficient absorption of essential metabolites such as phosphate, uric acid, glucose, amino acids, and low molecular weight proteins.
The first symptoms of Fanconi syndrome in Basenjis are exhibited around 3 to 7 years of age. Clinical signs are excessive drinking (polydipsia), excessive urination (polyuria), and glucose in the urine (glucosuria) because the kidneys are unable to conserve water. Other symptoms are also weight loss and poor hair coat. If the disorder is left untreated for a longer time, due to the loss of nutrients and electrolytes in the urine, muscle wasting, acidosis, and poor condition will develop. In case of the rapid progress of the disorder into kidney failure, signs such as poor appetite, extreme loss of weight, lethargy, vomiting, and pale gums due to anemia will appear. Due to glucose in the urine, affected dogs are prone to urinary tract infections. When untreated, the affected dog will eventually die from the disorder. If the disorder is treated on time, individual affected dogs can do well with their condition. Since affected dogs have urinary leakage, to determine whether the dog is affected, urine glucose test strips are used. Those test strips show the presence or absence of glucose in the urine. Veterinarian examinations include urine-specific gravity, glucosuria with normoglycemia, phosphaturia, and aminoaciduria.
Fanconi Syndrome Basenji type (FS) is caused by a mutation in the FAN1 gene (Fanconi anemia-associated nuclease 1), which is a part of the myotubularin gene family of tyrosine phosphatases. Gene name has been proposed because FAN1 protein interacts with Fanconi anemia (FA) pathway proteins. FA and FS in Basenjis are caused by a mutation in the same gene, but these two disorders are distant. This mutation causes FAN1 inactivation, which results in hyper-sensitization of the proximal tubule cells to low concentrations of heavy metals in FS-affected Basenjis. Since affected dogs are differently exposed to environmental toxins, this explains the wide range of age of onset for Fanconi syndrome in Basenjis. The disorder is inherited as an autosomal recessive trait. Healthy parents of an affected dog are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Farias, F. H. G. (2011.): MOLECULAR GENETIC STUDIES OF CANINE INHERITED DISEASES. A dissertation presented to the Faculty of the Graduate School University of Missouri.
Hooper, AN, et al. (2011.): Fanconi syndrome in four non-basenji dogs exposed to chicken jerky treats. J Am Anim Hosp Assoc. 47(6): e178-87. doi: 10.5326/JAAHA-MS-5602.