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Acute Respiratory Distress Syndrome (ARDS)
| Acronym: | ARDS |
| Gene: | ANLN |
| Mutation: | c.31C>T |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Acute respiratory distress syndrome (ARDS) is an inherited respiratory disorder that affects the Dalmatian dog breed. The genetic cause of ARDS in the Dalmatian dog breed has been identified, which enables a recognition of carriers and certain diagnostics of affected dogs. Other than dogs, ARDS has been also recognized in other species, including humans. Generally, ARDS is referred to as acute, life-threatening respiratory failure with a high mortality rate. Among dogs, the lethal outcome of ARDS reaches almost 100%. Except for genetics, other factors that contribute to the development of ARDS have been established. Primary factors cause direct injury to the lung; such as aspiration pneumonia, pulmonary contusions, or inhalation of harmful gases. Secondary factors cause the injury of the lungs through the activation of systemic inflammation mechanisms. Such factors are sepsis, pancreatitis, parvovirus enteritis, nonthoracic trauma, thermal burns, or paraquat ingestion.
General symptoms of ARDS in dogs are difficulty breathing, coughing, nasal discharge, fever, blue discoloration of the skin (cyanosis), or other signs related to the underlying disease. Pulmonary manifestations include multiple foci of marked atypical hyperplasia, patchy ongoing fibrosis with myofibroblastic metaplasia, smooth muscle hyperplasia, and sometimes hyperplasia of type II pneumocytes, as well as acute alveolar edema. Diagnosis is based on presenting clinical signs, thoracic radiographs, and exclusion of other causes of respiratory disease. Radiographs may show pericardial effusion, thoracic effusion, air bronchograms, and free air within the lung cavity. A differential diagnosis would include pulmonary interstitial fibrosis, chronic bronchitis, kennel cough, tracheal collapse, bronchomalacia, and bronchial carcinoma.
Acute respiratory distress syndrome (ARDS) in Dalmatian dogs is caused by a mutation in the ANLN gene. The mutation causes the production of a truncated protein, which abolishes the protein’s function. In affected dogs, ANLN protein is completely absent in the lungs, the predominant site of this protein’s expression. ANLN is crucial in cell division and in the assembly of intercellular junctions. Histopathological examination reveals disorganized bronchiolar epithelial regeneration and disturbed alveolar epithelial regeneration in affected dogs, which is due to improper ANLN function. The disorder is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show the ARDS symptoms. When mating two carriers (heterozygotes) 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:
Saila Holopainen, Marjo K. Hytönen, Pernilla Syrjä, Meharji Arumilli, Anna-Kaisa Järvinen, Minna Rajamäki, Hannes Lohi. ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs. PLOS Genetics, 2017; 13 (2): e1006625 DOI: 10.1371/journal.pgen.1006625