DNA screening for Lafora's disease in miniature wire‐haired dachshunds

Sainsbury, R. M.

doi:10.1136/vr.g7417

Cited by 7 publications

(5 citation statements)

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“…Of these, only NCL and LD have so far been identified in dogs (Awano et al ). The associated myoclonic jerks frequently involve head and thoracic limbs (Gredal et al , Sainsbury ). In our cases, photosensitive whole‐body myoclonus, sleep myoclonus and generalised seizures were also present.…”

Section: Discussionmentioning

confidence: 76%

NHLRC1 repeat expansion in two beagles with Lafora disease

Hajek¹,

Kettner

Šimerdová

et al. 2016

J of Small Animal Practice

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Lafora disease is a fatal genetic disorder with neurotoxic deposits of malformed insoluble glycogen. In humans it is caused by genetic variants in the EPM2A or NHLRC1 genes. There is a known sequence variant in Miniature Wirehaired Dachshunds but not in different dog breeds, including in Beagle dogs in which the disease is relatively commonly reported. This case report describes the causative defect in two affected Beagles, namely the same massive expansion as in Miniature Wirehaired Dachshunds of a 12-nucleotide repeat sequence that is unique to the canine NHLRC1 gene. This is the first sequence variant described in Beagles with Lafora disease, and so far the only Lafora disease genetic variant in dogs.

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Section: Discussionmentioning

confidence: 76%

NHLRC1 repeat expansion in two beagles with Lafora disease

Hajek¹,

Kettner

Šimerdová

et al. 2016

J of Small Animal Practice

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“…Chondrodystrophy is associated with the expression of a retrogene encoding fibroblast growth factor 4 (FGF4) located on chromosome 18 [11]; however, a continuous spectrum of disc degeneration and IVDE/IVDP is seen both among and within chondrodystrophic breeds, suggesting a multi-factorial aetiology involving cumulative effects of several genes and environmental interactions [10]. The Dachshund’s predisposition to IVDD has been demonstrated to be highly heritable [12, 13]; however, reducing the incidence of IVDD is not as simple as devising genetic tests of susceptibility, as has been successfully developed for Lafora’s disease, an autosomal recessive neurological disorder in Miniature Wirehaired Dachshunds [14, 15]. In contrast, IVDD is likely a polygenic disorder with many environmental influences.…”

Section: Introductionmentioning

confidence: 99%

DachsLife 2015: an investigation of lifestyle associations with the risk of intervertebral disc disease in Dachshunds

Packer

Seath²,

O’Neill

et al. 2016

Canine Genet Epidemiol

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BackgroundIntervertebral disc disease (IVDD) represents a major problem in the Dachshund, with at a relative risk of IVDD 10–12 times higher than other breeds, and an estimated 19–24 % of Dachshunds showing clinical signs related to IVDD during their lifetime. A variety of genetic, physical and lifestyle-related risk factors for IVDD have previously been identified, with some conflicting findings. As such, advising owners and breeders regarding best-practice for IVDD prevention is challenging at present. This study aimed to (i) estimate prevalence of IVDD in six Dachshund varieties, and (ii) identify risk factors associated with IVDD diagnosis from a wide variety of demographic, conformational, dietary, activity and exercise-related variables.ResultsA web-based survey “Dachs-Life 2015” was carried out from January-April 2015, with responses received for 2031 individual Dachshunds. Three-hundred and ten dogs were classed as Cases based on veterinary-diagnosis of IVDD, and 56 dogs were excluded from further analyses due to a lack of veterinary-diagnosis of their clinical signs. The remaining1665 dogs with no previous signs of IVDD were classified as Non-Cases. The overall prevalence of IVDD was 15.7 % (95 % CI: 14.1–17.3). Breed variety was significantly associated with IVDD risk, with the highest prevalence seen in the Standard Smooth-Haired (24.4 %, 95 % CI: 22.5–26.3) and lowest in the Standard Wire-Haired (7.1 %, 95 % CI: 6.0–8.2). Older dogs and neutered dogs were at increased odds of IVDD. Of the lifestyle risk factors, univariable analysis identified dogs that exercised for <30 min per day, were not allowed to jump on and off furniture, or were supplemented with glucosamine or chondroitin were at increased odds of IVDD, whereas dogs that exercised for more than 1 h per day, that were considered highly or moderately active by their owners, and those that showed at Open or Championship shows were at decreased odds of IVDD.ConclusionsIn line with previous reports, IVDD is commonly diagnosed in the Dachshund, with significant differences in prevalence between Dachshund varieties. Lifestyle risk factors were identified which are hypothesis-generating for future prospective studies, and can inform an evidence-based approach to mitigating IVDD risk for Dachshund owners and breeders.Electronic supplementary materialThe online version of this article (doi:10.1186/s40575-016-0039-8) contains supplementary material, which is available to authorized users.

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“…In a large study on miniature wirehaired dachshunds in the UK, nearly half of the dogs had at least 1 copy, and approximately 13% had 2 copies of the aberrant gene. 24 Recently, an owner-based retrospective study had demonstrated clinical phenotypes at early and late stage of the disease in dogs homozygous for the expanded EPM2B gene. 29 LD cases with EPM2B repeat expansion have also been reported in the basset hound and beagle.…”

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confidence: 99%

Accumulation of Laforin and Other Related Proteins in Canine Lafora Disease With EPM2B Repeat Expansion

et al. 2018

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Canine Lafora disease (LD) is an autosomal recessive genetic disorder causing nonfatal structural epilepsy, mainly affecting miniature wirehaired dachshunds. Repeat expansion in the EPM2B gene causes a functional impairment of the ubiquitin ligase malin which regulates glycogen metabolism. Abnormally structured glycogen accumulates and develop polyglucosan bodies predominantly in the central nervous system. The authors performed a comprehensive clinical, genetic, and pathological study of 4 LD cases affecting miniature wirehaired dachshund dogs with EPM2B repeat expansions, with systemic distribution of polyglucosan bodies and accumulation of laforin and other functionally associated proteins in the polyglucosan bodies. Myoclonic seizures first appeared at 7-9 years of age, and the dogs died at 14-16 years of age. Immunohistochemistry for calbindin revealed that the polyglucosan bodies were located in the cell bodies and dendritic processes of Purkinje cells. Polyglucosan bodies were also positive for laforin, hsp70, α/β-synuclein, ubiquitin, LC3, and p62. Laforin-positive polyglucosan bodies were located in neurofilament-positive neurons but not in GFAP-positive astrocytes. In nonneural tissues, periodic acid-Schiff (PAS)-positive polyglucosan bodies were observed in the heart, skeletal muscle, liver, apocrine sweat gland, and smooth muscle layer of the urinary bladder. In the skeletal muscle, polyglucosan bodies were observed only in type 1 fibers and not in type 2 fibers. The results indicate that although the repeat expansion of the EPM2B gene is specific to dogs, the immunohistochemical properties of polyglucosan body in canine LD are comparable to human LD. However, important phenotypic variations exist between the 2 species including the affected skeletal muscle fiber type.

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DNA screening for Lafora's disease in miniature wire‐haired dachshunds

Cited by 7 publications

References 1 publication

NHLRC1 repeat expansion in two beagles with Lafora disease

NHLRC1 repeat expansion in two beagles with Lafora disease

DachsLife 2015: an investigation of lifestyle associations with the risk of intervertebral disc disease in Dachshunds

Accumulation of Laforin and Other Related Proteins in Canine Lafora Disease With EPM2B Repeat Expansion

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