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Lethal acrodermatitis Bull Terrier Type (LAD)
| Acronym: | LAD |
| Gene: | MKLN1 |
| Mutation: | c.400+3A>C |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Lethal acrodermatitis Bull Terrier type is a severe, inherited skin disorder affecting Bull Terrier and Miniature Bull Terrier dog breed. The disorder has been for the first time described in 1986, and continuous research haven recently identified the causative mutation of LAD. A similar disorder recognized in human patients is known as acrodermatitis enteropathica and it is an inherited disorder of zinc metabolism. Unlike acrodermatitis enteropathica, in LAD-affected dogs, additional zinc intake does not help in reducing the symptoms. Several, but all researches have identified reduced zinc levels in LAD-affected dogs.
Lethal acrodermatitis-affected puppies start to show clinical symptoms already in the first weeks of life. LAD is characterized by skin lesions on the feet and on the face, diarrhea, bronchopneumonia, growth retardation, and immunodeficiency. The skin lesions appear as tightly adherent scales, erosions, or ulcerations with crusts, and are usually located on the feet, limbs, elbows, and muzzle. With the progression of symptoms, hyperkeratosis of the footpads and deformation of the nails appears. Due to immunodeficiency, dogs often suffer from skin infections with Malassezia or Candida. The coat shows color dilution in the pigmented areas. Affected dogs have an unusually arches hard palate, where food remains get stuck, decay, and contribute to a bad breath odor. Life expectancy is usually around 7 months of age, but the dogs are also commonly euthanized due to humane reasons, because of severe and painful lesions.
Lethal acrodermatitis Bull Terriers type (LAD) is caused by a frameshift in the canine MKLN1 gene. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the LEMP. At conception, when mating two carrier dogs, 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:
Bauer A, Jagannathan V, Hogler S, Richter B, McEwan NA, Thomas A, et al. (2018) MKLN1 splicing defect in dogs with lethal acrodermatitis. PLoS Genet 14(3): e1007264. https://doi.org/10.1371/journal.pgen.1007264