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Muscular Distrophy - Landseer Type (MDL)
| Acronym: | MDL |
| Gene: | COL6A1 |
| Mutation: | c.289G>T |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
| Method: |
Genetics and characteristics
Landseer Muscular dystrophy is a genetic disorder that causes progressive deterioration of the muscles in the Landseer dog breed. Generally, muscular dystrophy (MD) is a group of heterogeneous muscle diseases that weaken the musculoskeletal system and disrupt walking or moving abilities. Other than progressive skeletal muscle weakness, these disorders are characterized by defects in muscle proteins, and the death of muscle cells and tissue. Muscular dystrophy is known to affect dogs, cats, and humans. Among dogs, it is the most common in the Golden Retriever breed, but it differs in genetic background and mode of inheritance from muscular dystrophy in Landseer dogs. Other dog breeds affected with X-linked muscular dystrophy are Irish terriers, Pembroke Welsh Corgi, Samoyed, Rottweiler, Belgian Shepherd, Miniature Schnauzers, and others.
Collagen VI myopathies are a group of muscular dystrophies that are relatively less studied and understood than other groups of MDs. Collagen VI is an extracellular matrix protein, composed of three chains. The three chains together compose collagen VI molecules that further bind in complexes of dimers and tetramers. Through further binding, such molecules surround the basement membranes of fibers, binding components of the extracellular matrix and transferring mechanical and biochemical signals from the extracellular matrix to the muscle cell. The three subunits, or chains, that compose the collagen VI molecules are encoded by three genes, the COL6A1, COL6A2, and COL6A3 genes. Mutations within these genes can cause specific forms of muscular dystrophy.
Some of the common symptoms of Landseer Muscular Dystrophy are muscular weakness, excessive drooling, difficulty breathing, muscle spasms, difficulty moving the tongue, limb deformity, tremors, and gait abnormalities. Manipulation of the joints seems to be painful for the dog. Gait abnormalities include short, stridden gait in the thoracic and pelvic limbs. While standing dog’s back seems arched and the pelvic limbs are placed under the abdomen. On palpation, the muscles of the limbs seem to be atrophied. Articulations of the elbow, carpus, hip, and tarsus have a decreased range of motion. Elevated body temperature is possible and auscultation of the lungs can reveal hard sounds. Neurologically, the gag reflex seems to be reduced. Other neurological abnormalities have not been identified and affected dogs seem mentally alert. Creatine kinase activity is elevated, as well as leukocyte cell count in more severely affected dogs. Radiographic examination reveals generalized megaesophagus and aspiration pneumonia in the severely affected dogs. Affected dogs usually are euthanized due to the severity of the disorder at 5 months of age.
Landseer Muscular dystrophy is associated with a mutation in the COL6A1 gene. The disorder is inherited in an autosomal recessive manner. A dog can be clear, carrier, or affected. 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 muscular dystrophy. 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:
Steffen, F., Bilzer, T., Brands, J., Golini, L., Jagannathan, V., Wiedmer, M., Drögemüller, C., Drögemüller, M. & Leeb, T. (2015). A nonsense variant in COL6A1 in Landseer dogs with muscular dystrophy. G3: Genes| Genomes| Genetics, 5(12), 2611-2617.