OMIA:002324-9615 : Epilepsy, mitochondrial dysfunction and neurodegeneration, PITRM1-related in Canis lupus familiaris
Categories: Behaviour / neurological phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 618211 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2021
Inheritance: Hytönen et al. (2021): "Relatedness information of the affected dogs suggested an autosomal recessive mode of inheritance for the disease as all affected dogs were closely related, including affected littermates, both sexes were affected, and parents were unaffected."
Molecular basis: Hytönen et al. (2021): "Combined homozygosity mapping and genome sequencing revealed an in-frame 6-bp deletion in the nuclear-encoded pitrilysin metallopeptidase 1 (PITRM1) encoding for a mitochondrial protease involved in mitochondrial targeting sequence processing and degradation. The 6-bp deletion results in the loss of two amino acid residues in the N-terminal part of PITRM1 ... . Assessment of the mitochondrial function in the affected brain tissue showed a significant deficiency in respiratory chain function. The functional consequences of the mutation were modeled in yeast and showed impaired growth in permissive conditions and an impaired respiration capacity."
Clinical features: Hytönen et al. (2021): "The affected dogs develop normally until 6–12 weeks of life before the onset of rapidly worsening seizures, status epilepticus, and death."
Pathology: Hytönen et al. (2021): "Histopathological changes at autopsy were restricted to the brain. There was severe acute neuronal degeneration and necrosis diffusely affecting the grey matter throughout the brain with extensive intraneuronal mitochondrial crowding and accumulation of amyloid-β (Aβ)."
Breed: Parson Russell Terrier.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|PITRM1||pitrilysin metallopeptidase 1||Canis lupus familiaris||2||NC_051806.1 (32565906..32602813)||PITRM1||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1305||Parson Russell Terrier||Epilepsy, mitochondrial dysfunction and neurodegeneration||PITRM1||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||2||g.32188565_32188570del||c.175_180del||p.(L59_S60del)||ENSCAFT00000008673; ENSCAFT00000008673.4||2021||33835239|
|2021||Hytönen, M.K., Sarviaho, R., Jackson, C.B., Syrjä, P., Jokinen, T., Matiasek, K., Rosati, M., Dallabona, C., Baruffini, E., Quintero, I., Arumilli, M., Monteuuis, G., Donner, J., Anttila, M., Suomalainen, A., Bindoff, L.A., Lohi, H. :|
|In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration. Hum Genet 140:1593-1609, 2021. Pubmed reference: 33835239 . DOI: 10.1007/s00439-021-02279-y.|
- Created by Imke Tammen2 on 14 Apr 2021