One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

The partial 16s rRNA gene sequences of representative strains of two groups of anaerobic, gram-negative, pigmented, asaccharolytic, rod-shaped bacteria isolated from subgingival plaque of dogs with naturally occurring periodontal disease were determined. A comparative analysis of the rRNA sequence data revealed that the two groups of organisms represent previously unknown lines of descent within the genus Porphyromonus. On the basis of our phylogenetic findings and the phenotypic distinctiveness of the organisms, two new species, Porphyromonas cangingivalis and Porphyromonas cansulci, are proposed.

A new species, Porphyromonas canoris, is proposed for black-pigmented asaccharolytic strains isolated from subgingival plaque samples from dogs with naturally occurring periodontal disease. This bacterium is an obligately anaerobic, nonmotile, non-spore-forming, gram-negative, rod-shaped organism. On laked rabbit blood or sheep blood agar plates, colonies are light brown to greenish brown after 2 to 4 days of incubation and dark brown after 14 days of incubation. Colonies on egg yolk agar and on nonhemolyzed sheep blood agar are orange. The cells do not grow in the presence of 20% bile and have a guanine-plus-cytosine content of 49 to 51 mol%. The type strain is VPB 4878 (= NCTC 12835). The average levels of DNA-DNA hybridization between P. canoris strains and other members of the genus Porphyromonas are as follows: Porphyromonas gingivalis ATCC 33277T (T = type strain), 6.5%; Porphyromonas gingivalis cat strain VPB 3492, 5%; Porphyromonas endodontalis ATCC 35406T, 1%; Porphyromonas salivosa NCTC 1 1362T, 5%; and Porphyromonas circumdentaria NCTC 12469T, 6%. The level of hybridization between P. canoris NCTC 12835T DNA and Porphyromonas asaccharolytica ATCC 25260T DNA is 3%. P. canoris cells produce major amounts of acetic, propionic, isovaleric, and succinic acids and minor amounts of isobutyric and butyric acids as end products of metabolism in cooked meat medium. The major cellular fatty acid is 13-methyltetradecanoic acid (iso-C15:o). Glutamate and malate dehydrogenases are present, as are glucose-6-phosphate dehydrogenase activity (65.7 nmol mg of protein-' min-') and 6-phosphogluconate dehydrogenase activity (63.0 nmol mg of protein-' min-'). P. canoris cells do not agglutinate sheep erythrocytes but exhibit brick red fluorescence at 265 nm and produce catalase.During our investigation of the subgingival flora of 16 family-owned dogs with naturally occurring periodontitis, strictly anaerobic, nonsporing, gram-negative, asaccharolytic, rod-shaped organisms were found frequently (10,19,20). The results of morphological, biochemical, and API ZYM enzyme analyses placed several groups of these organisms in the genus Porphyromonas and DNA-DNA hybridization tests performed by using dot blot assays (12) showed that some of these organisms exhibited homology with either Porphyromonas gingivalis or Porphyromonas salivosa (unpublished data). However, the members of one group, which included 12 of the 259 phenotypically characterized isolates, did not hybridize in the DNA-DNA dot blot assay with any of the currently recognized species in the genus Porphyromonas. However, these strains had a range of characteristics which suggested that they could legitimately belong to the genus Porphyromonas. In this paper, we describe the results of DNA homology studies, a cellular fatty acid analysis, and an allozyme electrophoresis analysis and propose a new species, Porphyromonas canoris. MATERIALS AND METHODSBacterial strains. A total of 5 of the 12 strains described previously (10) as members of group C2 were examined in more d...

The clinical and radiological features and bacterial flora were studied in 16 small dogs with periodontitis. Gingival retraction, bleeding and alveolar bone loss were the most typical findings, whereas deep periodontal pockets were infrequently found. Periodontitis was frequently localised to certain regions of the dentition, most often in premolars or incisors. However, the deepest periodontal pockets were found in canine teeth. The mean pocket depth was 2·0 ± 0·4 mm (mean ± SD). The mean percentage of the sites with a pocket depth of more than 3 mm was 10·5 per cent. The mean occurrence of gingival bleeding after probing was 22·7 ± 12·7 per cent and the mean percentage of furcation lesions in multirooted teeth per dog was 46·0 ± 23·5 per cent. Tooth mobility was seen in 26·7 ± 13·3 per cent of the teeth. In each case subgingival plaque samples were taken for microbiological examination from two teeth with periodontitis and one healthy tooth. There was a clear difference between the diseased and healthy pockets in the detection frequency of the following Gram‐negative anaerobes: pigmented, non‐pigmented slime producing and fusiform rods. The counts of Gram‐negative pigmented, other non‐pigmented and fusiform rods as well as Gram‐positive cocci were clearly higher in the diseased pockets. Pigmented Gram‐negative rods (mainly asaccharolytic, Porphyromonas‐like species) were the most common finding in both diseased and healthy pockets.

A five-month-old male Labrador retriever presented with massive bilateral jaw and facial swelling. Ulcers were found on the buccal mucosa and palate, and the jaws were flexible on firm palpation. The dog could eat only soft food and was underweight. Renal hyperparathyroidism was diagnosed based on serum chemistry screen, parathormone concentration, radiological findings and histopathology. The dog was euthanatized because of an extremely poor prognosis.