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. 2023 Jan;37(1):216-222.
doi: 10.1111/jvim.16594. Epub 2022 Nov 25.

Spinocerebellar ataxia in the Bouvier des Ardennes breed is caused by a KCNJ10 missense variant

Kimberley Stee  1 , Mario Van Poucke  2 , Martí Pumarola  3 , Lise Geerinckx  4 , Iris Van Soens  5 , Sofie F M Bhatti  1 , Luc Peelman  2 , Ine Cornelis  1
Affiliations

Spinocerebellar ataxia in the Bouvier des Ardennes breed is caused by a KCNJ10 missense variant

Kimberley Stee et al. J Vet Intern Med. 2023 Jan.

Abstract

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.

Keywords: SAMS; SDCA; demyelinating myelopathy; hypermetric ataxia; intention tremors; spongy degeneration.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Pedigree information of the affected Bouvier des Ardennes family, drawn with the kinship2 package in RStudio. Squares represent males, circles females, black icons sampled dogs, gray icons nonsampled dogs, shaded icons cases, nonshaded icons healthy dogs, strikethrough icons deceased dogs. The KCNJ10 XM_545752.6:c.986T>C genotype is added for all sampled dogs
FIGURE 2
FIGURE 2
BAER recordings from dog 1 showing disappearance of waves III/VI and V
FIGURE 3
FIGURE 3
Histopathology of dog 1 at 8 weeks of age: (A and B) HE stain of the cerebellar cortex, vacuoles are restricted mainly to granular layer or intraneuronal in Purkinje cells; (C) GFAP immunopositives reactive astrocytes in the cerebellar cortex; (D) LFB stain of the spinal cord shows pale areas in the lateral and ventral funiculi
FIGURE 4
FIGURE 4
Histopathology of dog 2 at 7 months of age: (A and B) HE stain shows spongiosis in the cortical white matter, and infiltrating the cortical cerebellar granular layer. (C) IHC for Iba1 shows reactive microglial cells associated to spongiotic cerebellar area; (D) LFB stain of the spinal cord shows marked pallor of lateral and ventral funiculi. (E and F) IHC of the dorsal spinocerebellar tract of the cervical spinal cord. Absence or decreased immune positivity for NF200 (E) evidence loose of axonal component, some spheroids are also present. Marked immune positivity for Iba1 (F) in that area corresponding to reactive microgliosis is also evident
See this image and copyright information in PMC

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