A genome-wide linkage scan in German shepherd dogs localizes canine platelet procoagulant deficiency (Scott syndrome) to canine chromosome 27

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Gene (Impact Factor: 2.08). 10/2009; 450(1-2):70-5. DOI: 10.1016/j.gene.2009.09.016
Source: PubMed

ABSTRACT Scott syndrome is a rare hereditary bleeding disorder associated with an inability of stimulated platelets to externalize the negatively charged phospholipid, phosphatidylserine (PS). Canine Scott syndrome (CSS) is the only naturally occurring animal model of this defect and therefore represents a unique tool to discover a disease gene capable of producing this platelet phenotype. We undertook platelet function studies and linkage analyses in a pedigree of CSS-affected German shepherd dogs. Based on residual serum prothrombin and flow cytometric assays, CSS segregates as an autosomal recessive trait. An initial genome scan, performed by genotyping 48 dogs for 280 microsatellite markers, suggested linkage with markers on chromosome 27. Genotypes ultimately obtained for a total of 56 dogs at 11 markers on chromosome 27 revealed significant LOD scores for 2 markers near the centromere, with multipoint linkage indicating a CSS trait locus spanning approximately 14 cm. These results provide the basis for fine mapping studies to narrow the disease interval and target the evaluation of putative disease genes.

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    ABSTRACT: BACKGROUND: Platelet function defects are rare causes of bleeding diatheses; however, disease prevalence might be underestimated because diagnosis requires assessment of specific parameters of platelet activation. OBJECTIVES: The goal of this study was to characterize the clinical presentation of canine Scott syndrome (CSS), an intrinsic platelet function defect first identified in a closed colony of German Shepherds (GSD). ANIMALS: Eleven (n = 6 female) client-owned GSD affected with CSS that sought veterinary care for one or more episodes of abnormal bleeding. METHODS: Retrospective review of all cases of CSS diagnosed through the Comparative Coagulation Laboratory at Cornell University between 2005 and 2011. The diagnosis of CSS was based on 2 measures of platelet procoagulant activity: serum prothrombin consumption and flow cytometric detection of platelet phosphatidylserine externalization after in vitro activation. RESULTS: Postoperative hemorrhage was the most common sign of CSS, whereas petechiae were not found in any dog. Although most GSD responded to platelet transfusion, refractory epistaxis in 2 GSD was managed by nasal arterial embolization. The CSS trait was not restricted to a single pedigree of related GSD or to a single geographic region. CONCLUSIONS AND CLINICAL IMPORTANCE: Unlike thrombocytopenia and platelet aggregation defects, petechiae and other capillary hemorrhage are not typical features of CSS. After preliminary screening to rule out more common causes of hemorrhage, CSS should be considered in the differential diagnosis of recurrent hemorrhage in GSD, and potentially other breeds of dog. Definitive diagnosis of CSS requires specific tests of platelet procoagulant activity.
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