Deutsch
Hrvatski
Русский
Português
Spinal dysraphism – Weimaraner type
| Acronym: | Spinal dysraphism, NTD |
| Gene: | NKX2-8 |
| Mutation: | c.449delinsTT |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Spinal dysraphism or myelodysplasia is an inherited neurological disorder characterized by spinal cord malformation that affects the Weimaraner dog breed. The disorder is a part of a wider group of disorders, known as neural tube defects (NTDs). The NTDs are a result of the abnormal embryonal development of the neural tube, which with further development becomes the spinal column. Except for the Weimaraner, the disorder has been diagnosed also in other dog breeds, such as the Dalmatian, Rottweiler, West Highland White Terrier, German Shepherd, Golden Retriever, and Alaskan Malamute, but the causative mutation has been identified only in the Weimaraner, which enabled genetic testing for the disorder in this breed. Except for genetic causes, other forms of spinal dysraphism can be caused by infection, trauma, or tumor that will cause spinal cord damage.
Neurulation is a process that forms the vertebrate nervous system during embryonal development. It is divided into two stages, primary and secondary neurulation. Improper processes during the primary neurulation usually lead to open forms of NTDs, such as anencephaly and spina bifida. Symptoms of spinal dysraphism usually become visible as the puppy becomes mobile, which is usually between four and six weeks of age. Also, abnormal spinal reflexes may be noticed in newborn puppies. In general, clinical symptoms include abnormal spinal reflexes, symmetrical bunny hopping gait, wide-legged stance, overextended pelvic limbs, reduced proprioception, scoliosis, abnormal hair streams along the back, and gutter-like depression in the chest. For diagnostics of affected dogs, x-ray and cerebrospinal fluid analysis can be used.
Spinal dysraphism in Weimaraners is caused by a frameshift mutation of the NKX2-8 gene. The disorder is inherited as an autosomal recessive disorder. A homozygous dog possesses two copies of the causative gene and is affected. 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. There have been reported cases of spinal dysraphism in Weimaraners with reduced penetrance, but there was no evidence for it in recent research. The reason for this may be a possible second causative mutation within the breed, which may account for the previously reported inconsistent transmission.
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:
Safra, N., Bassuk, A. G., Ferguson, P. J., Aguilar, M., Coulson, R. L., Thomas, N., … Bannasch, D. L. (2013). Genome-Wide Association Mapping in Dogs Enables Identification of the Homeobox Gene, NKX2-8, as a Genetic Component of Neural Tube Defects in Humans. PLoS Genetics, 9(7), e1003646. http://doi.org/10.1371/journal.pgen.1003646