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Background In Belgian Malinois, a KCNJ10 variant causes progressive spinocerebellar degeneration. Hypothesis/Objectives Describe the clinical, diagnostic, pathological and genetic features of spinocerebellar degeneration in the Bouvier des Ardennes breed. Animals Five affected Bouvier des Ardennes puppies with spinocerebellar ataxia (SCA), 8 healthy related dogs, and 63 healthy unrelated Bouvier des Ardennes. Methods Sequential case study. Results Clinical signs started at 6 weeks of age in 1 puppy with severe signs of cerebellar disease, and at 7 to 10 weeks of age in the 4 remaining puppies with milder signs of spinocerebellar disease. The first puppy displayed severe intention tremors and rapidly progressive generalized hypermetric ataxia, whereas the 4 others developed a milder progressive SCA. Euthanasia after progression to nonambulatory status was performed by 8 weeks of age in the first puppy, and before 11 months of age in the 4 remaining puppies. Histopathology revealed cerebellar spongy degeneration and a focal symmetrical demyelinating myelopathy. All cases were homozygous for KCNJ10 XM_545752.6:c.986T>C(p.(Leu329Pro)), which is pathogenic for SCA with (or without) myokymia, seizures or both (SAMS) and spongy degeneration and cerebellar ataxia (SDCA) 1 in Belgian Malinois dogs. All sampled parents were heterozygous and none of the healthy dogs were homozygous for this recessive variant. This variant has an allele frequency of 15% in the 63 healthy dogs studied. Conclusions and Clinical Importance Inherited spinocerebellar degeneration also affects the Bouvier des Ardennes breed and is caused by a KCNJ10 variant. It can present with a spectrum of severity grades, ranging from severe cerebellar to milder spinocerebellar signs.

We describe the unique clinical presentation of a central nervous system neoplasm in a 6‐month‐old draft horse cross gelding. Based on the neurologic examination at admission, neurolocalization was most consistent with a mildly asymmetric cervical, multifocal, or diffuse myelopathy. Mild vestibular involvement also was considered, but no cranial nerve deficits were observed. The gelding was negative for Sarcocystis neurona or Neospora hughesi based on paired serum and cerebrospinal fluid (CSF) samples analyzed, with no evidence of cervical compression based on contrast myelography. The horse was euthanized because of progression of clinical signs. At necropsy, a mass was identified associated with the cerebellum, and histopathology was consistent with medulloblastoma, which has not been reported previously in the horse.

Background Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1 , each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers. Findings Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers. Conclusions A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as “hereditary ataxia” in Fox Terriers and “spinocerebellar ataxia with myokymia, seizures or both” in the Russell group of terriers.

Background Spinocerebellar ataxia also referred to as hereditary ataxia comprises different forms of progressive neurodegenerative diseases. A complex mode of inheritance was most likely in Parson Russell Terriers (PRT) and in Jack Russell Terriers (JRT). Recently, the missense mutation KCNJ10: c.627C > G was shown to be associated with the spinocerebellar ataxia (SCA) in JRT and related Russell group of terriers, whereas the missense mutation CAPN1: c.344G > A was associated with late onset ataxia (LOA) in PRT. Results We performed a genome-wide association study (GWAS) in PRT including 15 cases and 29 controls and found a statistically strong signal in the genomic region on dog chromosome 38 (CFA38) where KCNJ10 is located. We tested the CAPN1: c.344G > A and KCNJ10: c.627C > G (Transcript XM_545752.4) mutations in a sample of 77 PRT and 9 JRT from Germany as well as further 179 controls from 20 different dog breeds. All cases and controls genotyped carried the wild-type for the CAPN1: c.344G > A mutation. Among the PRT, 17/77 (22.1 %) dogs were homozygous for the mutant KCNJ10 allele and 22/77 (28.6 %) dogs were heterozygous. Three cases of PRT had the homozygous KCNJ10 wild-type. In JRT, 1/3 cases did show the mutant KCNJ10 allele homozygous. Thus, we sequenced the KCNJ10 exons with their adjacent regions from 10 PRT and 3 JRT including the animals with imperfect co-segregation of the c.627C > G mutation. We identified a total of 45 genetic variants within KCNJ10 . The most likely variant explaining the cases appeared a 1-bp-insertion in a C-stretch within exon 3 ( KCNJ10: g.22141027insC). In silico analysis showed that this indel may influence the regulation of gene expression. Conclusions In the present study, 16/21 cases of hereditary ataxia perfectly co-segregated with the KCNJ10: c.627C > G mutation. The CAPN1: c.344G > A mutation could not be validated and seems to be a rare variant in the samples screened. Screening KCNJ10 for further mutations did result in a genetic variant explaining 2 JRT cases but further 3 cases with a non-mutant homozygous c.627C > G genotype could not be resolved. Breeders have to be aware that DNA-testing for hereditary ataxia in PRT and JRT does not capture all cases of hereditary ataxia in these dog breeds. At least one further form of hereditary ataxia not yet resolved by a mutation may occur in PRT and JRT.

The diagnosis is supported by electrodiagnostic examination; the electromyogram reveals bursts of motor unit action potentials, sounding like marching soldiers, while brain auditory evoked potentials are typically delayed or absent.

Late onset of hereditary cerebellar cortical abiotrophy has been described in a large variety of canine breeds. In some reported conditions, the cerebellar lesion is combined with degeneration of other systems. Here we describe a new hereditary cerebellar cortical degeneration in eight adult American Staffordshire and Pit Bull Terriers. The neuronal degeneration in these animals not only affects Purkinje cells of the cerebellum but also certain thalamic nuclei. In addition, nerve cell loss appears to be associated with a lysosomal storage disease, which is restricted to the affected cell populations. The stored material was histologically and ultrastructurally identified as fluorescent lipopigment. Since animals were euthanized at various stages of the disease, it could be shown that lysosomal storage preceded neuronal loss. Selective involvement of restricted neuronal populations is highly unusual in ceroid lipofuscinoses. It remains to be determined if the present neurodegenerative disease is caused by a primary or secondary neuronal ceroid lipofuscinosis.

Preliminary pedigree analysis ( Robert and others 2004 ) indicates that common ancestors appear in the lineages of both affected and unaffected animals. [...]additional, extrinsic, rather than genetic, factors may underlie the propensity for both snow leopards and cheetahs to develop unusual diseases, such as hepatic veno-occlusive disease ( Van Den Ingh and others 1981 , Munson and Worley 1991 ) and encephalomyelopathy. [...]this case may be part of a spectrum of spinal cord degenerative disease in captive snow leopards described previously.

A 5-year-old Staffordshire terrier exhibited slowly progressive signs of cerebellar disease, including nystagmus and dysmetria. After a 30-month course, the dog was euthanized. Grossly, the cerebellum was small and comprised only 5% of the brain weight. Histopathological examination of the brain documented diffuse degeneration. Purkinje cells were most depleted, but granular cells and the molecular layer of cerebellum were also depleted. The history and necropsy examination were evidence of late-onset primary cerebellar degeneration.

Two domestic shorthair littermate kittens had signs of cerebellar dysfunction, first observed between seven and eight weeks of age; a third littermate was unaffected. The signs were progressive and the more severely affected kitten was euthanased after six days. A postmortem examination revealed no gross lesions but the kitten had cerebellar cortical degeneration with extensive loss of Purkinje cells. The second kitten was euthanased at 10 months of age with similar, though more pronounced, changes. One of the two kittens in the next litter of the same parents had similar clinical signs and histopathological findings. The lesions in the cerebellum are interpreted as probably due to genetically determined abiotrophy. In addition, the two older kittens had medullary neuronal changes interpreted as probable neuraxonal dystrophy, and focal vacuolation of the neuropil in the medulla and cervical spinal cord.

Eight Brittany Spaniel dogs, seven females and one male, between 7 and 14 years old presented with clinical neurological signs of spinocerebellar disease of about 6 months to 4 years duration. Clinically the dogs had a dramatic forward \"saluting\" movement of the thoracic limbs, hypermetria of the pelvic limbs, cerebellar ataxia and intention tremors. Terminally, dogs crawled in a crouched thoracic posture with neck extension. Lesions were confined to cerebellum, medulla oblongata and spinal cord. The most severe lesion was diffuse Purkinje cell loss with massive neurofilament accumulation in degenerating cells. There was some bilateral neuronal degeneration in the dorsal horns of the spinal cord and in the gracilis and cuneate nuclei. There was bilateral sporadic axonal degeneration in the dorsal columns and lateral and ventromedial areas of the spinal cord. The etiology of this syndrome was not determined.