Christen, Matthias; Gregor, Katharina M; Böttcher-Künneke, Ariane; Lombardo, Mara S; Baumgärtner, Wolfgang; Jagannathan, Vidhya; Puff, Christina; Leeb, Tosso (2024). Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis. (In Press). Animal genetics Wiley 10.1111/age.13441
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics |
UniBE Contributor: |
Christen, Matthias (A), Jagannathan, Vidya, Leeb, Tosso |
Subjects: |
500 Science > 590 Animals (Zoology) 600 Technology > 630 Agriculture |
ISSN: |
1365-2052 |
Publisher: |
Wiley |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
08 May 2024 08:33 |
Last Modified: |
09 May 2024 06:21 |
Publisher DOI: |
10.1111/age.13441 |
PubMed ID: |
38712841 |
Uncontrolled Keywords: |
Oryctolagus cuniculus Batten disease animal model hereditary disease neurology precision medicine |
BORIS DOI: |
10.48350/196605 |
URI: |
https://boris.unibe.ch/id/eprint/196605 |
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