Hereditary factor VII deficiency in the Alaskan Klee Kai dog.
BACKGROUND
Hereditary factor VII (FVII) deficiency is characterized as a mild bleeding disorder in Beagles, caused by a missense mutation in exon 5 of the FVII gene. An Alaskan Klee Kai dog with severe bleeding after trauma was diagnosed with FVII deficiency based on coagulation testing. Molecular analyses were undertaken to identify the genetic basis of the defect in this breed.


OBJECTIVE
FVII deficiency in Alaskan Klee Kai dogs is caused by a mutation in the FVII gene.


METHODS
Eighteen client-owned Alaskan Klee Kai.


METHODS
Coagulation screening tests and factor assays were performed to characterize the coagulopathy. All coding regions of the propositus' FVII gene were sequenced. Amplification of exon 5, sequencing, and Mnl I restriction digest experiments were performed to screen for a point mutation in the remaining 17 dogs.


RESULTS
FVII deficiency was diagnosed in 6 dogs with a median FVII activity (FVII: C) of 5% (reference range, 50 150%). All FVII-deficient Alaskan Klee Kai were homozygous for the same mutation as FVII-deficient Beagles (ie, a G to A transition), resulting in substitution of glycine 96 by glutamic acid. An overlap in the FVII: C values obtained from heterozygote and wild-type dogs precluded accurate detection of carriers without genetic screening.


CONCLUSIONS
FVII deficiency may be associated with a bleeding tendency and should be considered in Alaskan Klee Kai dogs with prolonged prothrombin times. Plasma FVII: C accurately identifies affected dogs, but deoxyribonucleic acid testing is required for identification of carriers.
Kaae
Jennifer A
JA
Department of Medical Sciences, School of Veterinary Medicine, University of' Wisconsin, Madison, WI, USA.
Callan
Mary Beth
MB
Brooks
Marjory B
MB
D000818:Animals; D001483:Base Sequence; D025861:Blood Coagulation Disorders, Inherited / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004283:Dog Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D005260:Female; D005838:Genotype; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D010314:Partial Thromboplastin Time / Q000662:veterinary; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011517:Prothrombin Time / Q000662:veterinary; D017422:Sequence Analysis, DNA
D005167:Factor VII; D004247:DNA