Neuronale Zeroidlipofuszinose bei einem adulten American Staffordshire Terrier

Nolte, Anna; Bello, Aimara; Drögemüller, Michaela; Leeb, Tosso; Brockhaus, Eva; Baumgärtner, Wolfgang; Wohlsein, P.

doi:10.15654/tpk-150766

Cited by 4 publications

(6 citation statements)

References 34 publications

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“…The histochemical and immunohistological results in the CNS are consistent with previously published reports on NCL in humans (Anderson et al, 2013) and other animal species (Ashwini et al, 2016;Cesta et al, 2006;Chalkley et al, 2014;Faller et al, 2016;Guo et al, 2015;Nibe et al, 2011;Nolte et al, 2016). The most prominent features in this case were the astrogliosis and loss of phosphorylated neurofilament throughout the CNS.…”

supporting

confidence: 91%

“…During the last two decades, veterinary medicine has made great progress concerning the description and genetic characterization of NCL. Different forms of NCL have been described in many domestic and wild animal species (Barker et al., 2023; Bond et al., 2013; Chalkley et al., 2014; Guo et al., 2019; Huber et al., 2020; Katz et al., 2020; Nicholas et al., 1995; Nittari et al., 2023; Nolte et al., 2016; Swier et al., 2022; Villani et al., 2019). Furthermore, disease‐causing genetic variants were discovered or experimentally induced in domestic animals for nine of the 14 different human NCL types (Table 1) (Huber et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

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Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis

Christen,

Gregor,

Böttcher‐Künneke

et al. 2024

Animal Genetics

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Neuronal ceroid lipofuscinoses (NCL) are among the most prevalent neurodegenerative disorders of early life in humans. Disease‐causing variants have been described for 13 different NCL genes. In this study, a refined pathological characterization of a female rabbit with progressive neurological signs reminiscent of NCL was performed. Cytoplasmic pigment present in neurons was weakly positive with Sudan black B and autofluorescent. Immunohistology revealed astrogliosis, microgliosis and axonal degeneration. During the subsequent genetic investigation, the genome of the affected rabbit was sequenced and examined for private variants in NCL candidate genes. The analysis revealed a homozygous ~10.7 kb genomic duplication on chromosome 15 comprising parts of the MFSD8 gene, NC_013683.1:g.103,727,963_103,738,667dup. The duplication harbors two internal protein coding exons and is predicted to introduce a premature stop codon into the transcript, truncating ~50% of the wild‐type MFSD8 open reading frame encoding the major facilitator superfamily domain containing protein 8, XP_002717309.2:p.(Glu235Leufs*23). Biallelic loss‐of‐function variants in MFSD8 have been described to cause NCL7 in human patients, dogs and a single cat. The available clinical and pathological data, together with current knowledge about MFSD8 variants and their functional impact in other species, point to the MFSD8 duplication as a likely causative defect for the observed phenotype in the affected rabbit.

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supporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis

Christen,

Gregor,

Böttcher‐Künneke

et al. 2024

Animal Genetics

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“…46 There are 4 clinically similar but genetically and biochemically distinct subtypes of MPS III, designated as IIIA to IIID in humans. In mice there is a fifth MPS III form (MPS IIIE), 38 which is suspected in dogs 47 and is as yet undiscovered in humans. In the aggregate, Sanfilippo syndrome has been documented to be the MPS type with the greatest incidence, at 1:72.9 thousand births, 43 and among the subtypes MPS IIIB is one of the most common subtypes with an incidence rate geographically ranging from 1 in every 139 000 to 500 000 live births.…”

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confidence: 99%

Temporospatial Development of Neuropathologic Findings in a Canine Model of Mucopolysaccharidosis IIIB

et al. 2020

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Mucopolysaccharidosis (MPS) IIIB is a neuropathic lysosomal storage disease characterized by the deficient activity of a lysosomal enzyme obligate for the degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The pathogenesis of neurodegeneration in MPS IIIB is incompletely understood. Large animal models are attractive for pathogenesis and therapeutic studies due to their larger size, outbred genetics, longer lifespan, and naturally occurring MPS IIIB disease. However, the temporospatial development of neuropathologic changes has not been reported for canine MPS IIIB. Here we describe lesions in 8 brain regions, cervical spinal cord, and dorsal root ganglion (DRG) in a canine model of MPS IIIB that includes dogs aged from 2 to 26 months of age. Pathological changes in the brain included early microscopic vacuolation of glial cells initially observed at 2 months, and vacuolation of neurons initially observed at 10 months. Inclusions within affected cells variably stained positively with PAS and LFB stains. Quantitative immunohistochemistry demonstrated increased glial expression of GFAP and Iba1 in dogs with MPS IIIB compared to age-matched controls at all time points, suggesting neuroinflammation occurs early in disease. Loss of Purkinje cells was initially observed at 10 months and was pronounced in 18- and 26-month-old dogs with MPS IIIB. Our results support the dog as a replicative model of MPS IIIB neurologic lesions and detail the pathologic and neuroinflammatory changes in the spinal cord and DRG of MPS IIIB-affected dogs.

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“…Fluorescent lipopigment is present in both degenerating Purkinje cells and thalamic neurons. 108 This disease was initially described as a CCD, 105 , 106 , 107 , 109 but is currently recognized as a NCL, 34 , 108 , 110 even though some authors believe it should be reclassified as a mucopolysaccharidosis. 111 …”

Section: Multifocal Degenerations With Predominant (Spino)cerebellar ...mentioning

confidence: 99%

Phenotypic and genetic aspects of hereditary ataxia in dogs

Stee

Poucke

Lowrie³

et al. 2023

Veterinary Internal Medicne

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Hereditary ataxias are a large group of neurodegenerative diseases that have cerebellar or spinocerebellar dysfunction as core feature, occurring as an isolated sign or as part of a syndrome. Based on neuropathology, this group of diseases has so far been classified into cerebellar cortical degenerations, spinocerebellar degenerations, cerebellar ataxias without substantial neurodegeneration, canine multiple system degeneration, and episodic ataxia. Several new hereditary ataxia syndromes are described, but most of these diseases have similar clinical signs and unspecific diagnostic findings, wherefore achieving a definitive diagnosis in these dogs is challenging. Eighteen new genetic variants associated with these diseases have been discovered in the last decade, allowing clinicians to reach a definitive diagnosis for most of these conditions, and allowing breeding schemes to adapt to prevent breeding of affected puppies. This review summarizes the current knowledge about hereditary ataxias in dogs, and proposes to add a "multifocal degenerations with predominant (spino)cerebellar component" category regrouping canine multiple system degeneration, new hereditary ataxia syndromes that do not fit in 1 of the previous categories, as well as specific neuroaxonal dystrophies and lysosomal storage diseases that cause major (spino)cerebellar dysfunction.

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Neuronale Zeroidlipofuszinose bei einem adulten American Staffordshire Terrier

Cited by 4 publications

References 34 publications

Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis

Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis

Temporospatial Development of Neuropathologic Findings in a Canine Model of Mucopolysaccharidosis IIIB

Phenotypic and genetic aspects of hereditary ataxia in dogs

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