Rietmann, Stefan Jonas (2024). Intragenic duplication disrupting the reading frame of MFSD8 in Small Swiss Hounds with neuronal ceroid lipofuscinosis. (Thesis). Universität Bern, Bern
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Abstract
Neuronal ceroid lipofuscinosis (NCL) represents a heterogenous group of lysosomal storage disorders resulting in progressive neurodegeneration. We investigated two Small Swiss Hound littermates with neurological signs starting around the age of twelve months. Both dogs had to be euthanized a few months after the onset of the disease due to the severity of their clinical signs. Pathological investigation of one affected dog revealed cerebral and cerebellar atrophy with cytoplasmic accumulation of autofluorescent material in degenerating neurons. The clinical signs and characteristic histopathology led to a tentative diagnosis of NCL. In the genetic investigation a duplication of 18,819 bp within the MFSD8 gene was revealed. The duplication breakpoints were predicted to disrupt the reading frame of the gene. Both affected dogs carried the duplication in a homozygous state and there was perfect cosegregation of the genotypes with the phenotype in a large pedigree, consistent with autosomal recessive inheritance. MFSD8 loss-of-function variants are a known cause of NCL7 in human patients, dogs and other mammalian species. The existing knowledge on MFSD8 together with the experimental data strongly suggests that the identified intragenic MFSD8 duplication caused the disease in the Small Swiss Hounds. These results allow to refine their diagnosis to NCL7 and enable genetic testing in the breed to avoid further unintentional carrier x carrier matings.
| Item Type: | Thesis |
|---|---|
| Dissertation Type: | Single |
| Date of Defense: | 27 August 2024 |
| Subjects: | 500 Science > 590 Animals (Zoology) 600 Technology > 610 Medicine & health |
| Institute / Center: | 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics |
| Depositing User: | Hammer Igor |
| Date Deposited: | 18 Feb 2025 15:54 |
| Last Modified: | 18 Feb 2025 15:54 |
| URI: | https://boristheses.unibe.ch/id/eprint/5829 |
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