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• W4386325466 endingPage "1746" @default.
• W4386325466 startingPage "1746" @default.
• W4386325466 abstract "A 7-month-old Doberman Pinscher dog presented with progressive neurological signs and brain atrophy suggestive of a hereditary neurodegenerative disorder. The dog was euthanized due to the progression of disease signs. Microscopic examination of tissues collected at the time of euthanasia revealed massive accumulations of vacuolar inclusions in cells throughout the central nervous system, suggestive of a lysosomal storage disorder. A whole genome sequence generated with DNA from the affected dog contained a likely causal, homozygous missense variant in MAN2B1 that predicted an Asp104Gly amino acid substitution that was unique among whole genome sequences from over 4000 dogs. A lack of detectable α-mannosidase enzyme activity confirmed a diagnosis of a-mannosidosis. In addition to the vacuolar inclusions characteristic of α-mannosidosis, the dog exhibited accumulations of autofluorescent intracellular inclusions in some of the same tissues. The autofluorescence was similar to that which occurs in a group of lysosomal storage disorders called neuronal ceroid lipofuscinoses (NCLs). As in many of the NCLs, some of the storage bodies immunostained strongly for mitochondrial ATP synthase subunit c protein. This protein is not a substrate for α-mannosidase, so its accumulation and the development of storage body autofluorescence were likely due to a generalized impairment of lysosomal function secondary to the accumulation of α-mannosidase substrates. Thus, it appears that storage body autofluorescence and subunit c accumulation are not unique to the NCLs. Consistent with generalized lysosomal impairment, the affected dog exhibited accumulations of intracellular inclusions with varied and complex ultrastructural features characteristic of autophagolysosomes. Impaired autophagic flux may be a general feature of this class of disorders that contributes to disease pathology and could be a target for therapeutic intervention. In addition to storage body accumulation, glial activation indicative of neuroinflammation was observed in the brain and spinal cord of the proband." @default.
• W4386325466 created "2023-09-01" @default.
• W4386325466 creator A5005112800 @default.
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• W4386325466 date "2023-08-31" @default.
• W4386325466 modified "2023-10-08" @default.
• W4386325466 title "A Homozygous MAN2B1 Missense Mutation in a Doberman Pinscher Dog with Neurodegeneration, Cytoplasmic Vacuoles, Autofluorescent Storage Granules, and an α-Mannosidase Deficiency" @default.
• W4386325466 cites W1509414328 @default.
• W4386325466 cites W1560087770 @default.
• W4386325466 cites W1570427382 @default.
• W4386325466 cites W1574600379 @default.
• W4386325466 cites W1967979773 @default.
• W4386325466 cites W1974324509 @default.
• W4386325466 cites W1976498837 @default.
• W4386325466 cites W1980742849 @default.
• W4386325466 cites W1980777735 @default.
• W4386325466 cites W1983547981 @default.
• W4386325466 cites W1985349046 @default.
• W4386325466 cites W1985559749 @default.
• W4386325466 cites W1990200256 @default.
• W4386325466 cites W1996185349 @default.
• W4386325466 cites W1998448615 @default.
• W4386325466 cites W2000915110 @default.
• W4386325466 cites W2003726432 @default.
• W4386325466 cites W2005843015 @default.
• W4386325466 cites W2010293058 @default.
• W4386325466 cites W2021341670 @default.
• W4386325466 cites W2026420637 @default.
• W4386325466 cites W2028650990 @default.
• W4386325466 cites W2036502061 @default.
• W4386325466 cites W2038244231 @default.
• W4386325466 cites W2039102735 @default.
• W4386325466 cites W2039434580 @default.
• W4386325466 cites W2040301614 @default.
• W4386325466 cites W2044549622 @default.
• W4386325466 cites W2044650614 @default.
• W4386325466 cites W2045480080 @default.
• W4386325466 cites W2047099465 @default.
• W4386325466 cites W2047277088 @default.
• W4386325466 cites W2048235713 @default.
• W4386325466 cites W2054595666 @default.
• W4386325466 cites W2055262857 @default.
• W4386325466 cites W2056084922 @default.
• W4386325466 cites W2057919708 @default.
• W4386325466 cites W2059663517 @default.
• W4386325466 cites W2061166811 @default.
• W4386325466 cites W2069197202 @default.
• W4386325466 cites W2070247857 @default.
• W4386325466 cites W2071576107 @default.
• W4386325466 cites W2073170807 @default.
• W4386325466 cites W2082038511 @default.
• W4386325466 cites W2095706874 @default.
• W4386325466 cites W2100196074 @default.
• W4386325466 cites W2103377481 @default.
• W4386325466 cites W2103894947 @default.
• W4386325466 cites W2104904689 @default.
• W4386325466 cites W2106775189 @default.
• W4386325466 cites W2109078396 @default.
• W4386325466 cites W2124983243 @default.
• W4386325466 cites W2128579664 @default.
• W4386325466 cites W2129763897 @default.
• W4386325466 cites W2132754272 @default.
• W4386325466 cites W2133280072 @default.
• W4386325466 cites W2133615119 @default.
• W4386325466 cites W2136284882 @default.
• W4386325466 cites W2139620504 @default.
• W4386325466 cites W2141151427 @default.
• W4386325466 cites W2264979642 @default.
• W4386325466 cites W2269555972 @default.
• W4386325466 cites W2270229351 @default.
• W4386325466 cites W2328590583 @default.
• W4386325466 cites W2382534732 @default.
• W4386325466 cites W2396808893 @default.
• W4386325466 cites W2415970754 @default.
• W4386325466 cites W2427690353 @default.
• W4386325466 cites W2566371625 @default.
• W4386325466 cites W2574334611 @default.
• W4386325466 cites W2735931993 @default.
• W4386325466 cites W2747405063 @default.
• W4386325466 cites W2753495793 @default.
• W4386325466 cites W2768724720 @default.
• W4386325466 cites W2775704554 @default.
• W4386325466 cites W2781686070 @default.
• W4386325466 cites W2898107549 @default.
• W4386325466 cites W2903972797 @default.
• W4386325466 cites W2913637686 @default.
• W4386325466 cites W2914700253 @default.
• W4386325466 cites W2922746369 @default.
• W4386325466 cites W2929961692 @default.
• W4386325466 cites W2936319629 @default.
• W4386325466 cites W2936894539 @default.

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