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Spondylocostal Dysostosis – Comma Defect
| Acronym: | SCD |
| Gene: | HES7 |
| Mutation: | c.126delG |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Spondylocostal Dysostosis (Comma Defect) is an inherited axial skeleton growth disorder that affects the Miniature Schnauzer dog breed. The disorder is characterized by truncal shortening, extensive hemivertebrae, and rib anomalies, such as malalignment, fusion, and reduction in number. Spondylocostal dysostosis also affects human patients, but the name Comma Defect is referred only to the canine form of this disorder, due to the gross anatomical shape of the abnormal pups. The disorder has been associated with mutations in the notch signaling pathway genes.
During embryogenesis, the proper formation of somites is essential for the normal development of the axial skeleton, skeletal muscles, and dermis in later development. This formation is controlled by the expression of numerous genes, in which the Notch signaling pathway genes play a crucial role. Mutations in the genes of the Notch signaling pathway result in improper somites formation and consequently failed in the normal development of the axial skeleton. The affected puppies, due to the severity of skeletal abnormalities, are stillborn or die briefly after birth. Examination of the affected puppies reveals a reduction in body length compared to healthy littermates. Hind limbs are much shorter than front limbs, which gives a comma-like morphology to the body. Abnormalities like umbilical hernia and cleft hard palate are also possible in affected pups. Mortality of the puppies is likely due to impaired respiratory function as a result of a truncal shortening and rib fusion.
Spondylocostal Dysostosis (Comma Defect) in Miniature Schnauzers is caused by a mutation in the HES7 gene. Expression of the HES7 is specific to the presomitic mesoderm and is controlled by the Notch signaling pathway. Hes7-deficient mice have severe defects of the axial skeleton, which confirms the essential role of Hes7 in somitogenesis. Various HES7 mutations have been detected also in Spondylocostal Dysostosis affected human patients. The disorder is inherited in an autosomal recessive manner. Homozygotes are affected and heterozygotes have no symptoms. When mating two carriers (heterozygotes), 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 is no cure for this disorder, and the only way to prevent it is to breed dogs that are not carriers of the mutation. Defected genes for an autosomal recessive disease can be passed for many generations without affected individuals occurring until two carriers are bred to one another. DNA testing for Spondylocostal Dysostosis (Comma Defect) in Miniature Schnauzers enables recognition carriers and prevents unnecessary neonatal losses.
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:
Willet CE, Makara M, Reppas G, Tsoukalas G, Malik R, Haase B, et al. (2015) Canine Disorder Mirrors Human Disease: Exonic Deletion in HES7 Causes Autosomal Recessive Spondylocostal Dysostosis in Miniature Schnauzer Dogs. PLoS ONE 10(2): e0117055. doi:10.1371/journal.pone.0117055