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Nemaline Myopathy American Bulldog Type (NM)
| Acronym: | NM |
| Gene: | NEB |
| Mutation: | g.52734272G>T |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Nemaline myopathy (NM) is an inherited muscle disorder characterized by the presence of rod bodies in the skeletal muscle fibers. Canine form of nemaline myopathy has been diagnosed in the American Bulldog, Border Collie, and Schipperke, but the causative mutation has been identified only in the American Bulldog dog. Except in dogs, the disorder has been recognized also in cats and humans, while in humans it makes the most common human congenital myopathy, accounting for 17% of cases. An adult form of NM has been diagnosed in several mix-breed dogs, but as in humans, adult occurring forms of NM are not caused by genetic heritage. To exclude other possible diseases with similar symptoms, when diagnosing NME differential diagnoses for polymyositis, Duchenne muscular dystrophy, and muscle parasites are included.
Clinical symptoms in the affected dog include generalized muscle weakness, exercise intolerance, and tremors which usually start around 2 months of age. The owners often report that their dog from an early age is constantly shaking and is reluctant to exercise. The affected dog has generalized atrophy, and the myopathy is relatively non-progressive. Muscle examination reveals atrophy of the cervical and dorsal thoracic limb muscles as well as hypertrophy of the triceps muscles. Serum creatine kinase activities were mildly elevated. Compared to the healthy muscle, affected Americal Bulldogs showed marked variability in myofiber size and present generalized atrophy. In most of the muscles, rod-like inclusion bodies could be found, which are not present in a healthy muscle.
Nemaline myopathy in American Bulldogs (NM) is caused by a nonsense mutation in the NEB gene. NEB gene codes for nebulin protein (NEB) whose role is to stabilize the actin thin filament of skeletal muscle sarcomeres and is crucial for proper muscle contraction. This specific mutation is directly connected to canine NM disorder, but a different mutation in the same gene has been also connected with the primary angle-closure glaucoma in Basset hounds. Nemaline myopathy in American Bulldogs (NM) is inherited in an autosomal recessive pattern. Healthy parents of the 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 NM. 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:
Evans, J. M. et al (2016) Exome sequencing reveals a nebulin nonsense mutation in a dog model of nemaline myopathy. Mamm Genome. 27(9-10):495-502. doi: 10.1007/s00335-016-9644-9.
Delauche AJ et al (1998) Nemaline rods in canine myopathies: 4 case reports and literature review. J Vet Intern Med 12(6):424-430
Nakamura RK et al (2012) Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism. J Small Anim Pract 53(6):357-360