title: Magnetic resonance imaging and genetic investigation of a case of Rottweiler leukoencephalomyelopathy.
abstract: BACKGROUND
  Leukoencephalomyelopathy is an inherited neurodegenerative disorder that affects the white matter of the spinal cord and brain and is known to occur in the Rottweiler breed. Due to the lack of a genetic test for this disorder, post mortem neuropathological examinations are required to confirm the diagnosis. Leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate levels is a rare, autosomal recessive disorder in humans that was recently described to have clinical features and magnetic resonance imaging (MRI) findings that are similar to the histopathologic lesions that define leukoencephalomyelopathy in Rottweilers. Leukoencephalopathy with brain stem and spinal cord involvement is caused by mutations in the DARS2 gene, which encodes a mitochondrial aspartyl-tRNA synthetase. The objective of this case report is to present the results of MRI and candidate gene analysis of a case of Rottweiler leukoencephalomyelopathy to investigate the hypothesis that leukoencephalomyelopathy in Rottweilers could serve as an animal model of human leukoencephalopathy with brain stem and spinal cord involvement.
  
  
  METHODS
  A two-and-a-half-year-old male purebred Rottweiler was evaluated for generalised progressive ataxia with hypermetria that was most evident in the thoracic limbs. MRI (T2-weighted) demonstrated well-circumscribed hyperintense signals within both lateral funiculi that extended from the level of the first to the sixth cervical vertebral body. A neurodegenerative disorder was suspected based on the progressive clinical course and MRI findings, and Rottweiler leukoencephalomyelopathy was subsequently confirmed via histopathology. The DARS2 gene was investigated as a causative candidate, but a sequence analysis failed to identify any disease-associated variants in the DNA sequence.
  
  
  CONCLUSIONS
  It was concluded that MRI may aid in the pre-mortem diagnosis of suspected cases of leukoencephalomyelopathy. Genes other than DARS2 may be involved in Rottweiler leukoencephalomyelopathy and may also be relevant in human leukoencephalopathy with brain stem and spinal cord involvement.
authors.affiliation: Department of Veterinary Clinical Sciences Ludwig-Maximilians-Universitaet, Neurology Service, Clinic of Small Animal Medicine, Munich, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hirschvogel
authors.forename: Kaspar
authors.initials: K
authors.lastname: Matiasek
authors.forename: Katharina
authors.initials: K
authors.lastname: Flatz
authors.forename: Michaela
authors.initials: M
authors.lastname: Drögemüller
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
authors.forename: Bärbel
authors.initials: B
authors.lastname: Reiner
authors.forename: Andrea
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001226:Aspartate-tRNA Ligase / Q000235:genetics; D001259:Ataxia / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D001921:Brain / Q000473:pathology; D004283:Dog Diseases / Q000235:genetics / Q000473:pathology*; D004285:Dogs; D056784:Leukoencephalopathies / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D008279:Magnetic Resonance Imaging / Q000662:veterinary; D008297:Male; D013116:Spinal Cord / Q000473:pathology; D013118:Spinal Cord Diseases / Q000235:genetics / Q000473:pathology / Q000662:veterinary*
chemical_list: D001226:Aspartate-tRNA Ligase