OMIA:001947-9615 : Cerebellar hypoplasia, VLDLR-associated in Canis lupus familiaris (dog)
Categories: Nervous system phene
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: 2015
Species-specific name: Dandy-Walker-like malformation
Species-specific symbol: DWLM
Mapping: By conducting a GWAS involving 9 affected and 11 normal Eurasier dogs, each genotyped with the Illumina HD SNP chip (yielding 110,848 informative markers), Gerber et al. (2015) mapped this disorder to the 90.9–94.2 Mb region of canine chromosome CFA1 (CanFam 3 assembly). Subsequent homozygosity mapping confirmed this candidate region.
Molecular basis: Comparison of the whole-genome sequence of one of the affected Eurasier dogs with similar data from 47 dogs of other breeds enabled Gerber et al. (2015) to narrow the candidate field down to 4 non-synonymous variants. Genotyping of these four variants in 34 Eurasier dogs revealed only one variant that co-segregated perfectly with the disorder allele: a single bp deletion in VLDLR (c.1713delC) which "results in a frameshift and premature stop codon. It is predicted to truncate more than a third of the encoded very low density lipoprotein receptor (p.W572Gfs*10)".
Clinical features: This disorder in Eurasier dogs was described by Bernardino et al. (2015): "A uniform cerebellar malformation characterized by consistent absence of the caudal portions of the cerebellar vermis and, to a lesser degree, the caudal portions of the cerebellar hemispheres in association with large retrocerebellar fluid accumulations was recognized in 14 closely related Eurasier dogs. Hydrocephalus was an additional feature in some dogs. All dogs displayed non-progressive ataxia, which had already been noted when the dogs were 5 - 6 weeks old. The severity of the ataxia varied between dogs, from mild truncal sway, subtle dysmetric gait, dysequilibrium and pelvic limb ataxia to severe cerebellar ataxia in puppies and episodic falling or rolling. Follow-up examinations in adult dogs showed improvement of the cerebellar ataxia and a still absent menace response. Epileptic seizures occurred in some dogs. The association of partial vermis agenesis with an enlarged fourth ventricle and an enlarged caudal (posterior) fossa resembled a Dandy-Walker-like malformation in some dogs".
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|VLDLR||very low density lipoprotein receptor||Canis lupus familiaris||1||NC_051805.1 (91786552..91821587)||VLDLR||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|
|917||Eurasier||Cerebellar hypoplasia, VLDLR-associated||VLDLR||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||1||g.91266144del||c.1713del||p.(W572Gfs*10)||NM_001286978.1; NP_001273907.1; published as c.1713delC||2015||25668033||Genomic position in CanFam3.1 provided by Robert Kuhn|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2015||Bernardino, F., Rentmeister, K., Schmidt, M.J., Bruehschwein, A., Matiasek, K., Matiasek, L.A., Lauda, A., Schoon, H.A., Fischer, A. :|
|Inferior cerebellar hypoplasia resembling a dandy-walker-like malformation in purebred eurasier dogs with familial non-progressive ataxia: a retrospective and prospective clinical cohort study. PLoS One 10:e0117670, 2015. Pubmed reference: 25668516 . DOI: 10.1371/journal.pone.0117670.|
|Gerber, M., Fischer, A., Jagannathan, V., Drögemüller, M., Drögemüller, C., Schmidt, M.J., Bernardino, F., Manz, E., Matiasek, K., Rentmeister, K., Leeb, T. :|
|A deletion in the VLDLR gene in Eurasier dogs with cerebellar hypoplasia resembling a Dandy-Walker-like malformation (DWLM). PLoS One 10:e0108917, 2015. Pubmed reference: 25668033 . DOI: 10.1371/journal.pone.0108917.|
- Created by Frank Nicholas on 05 Mar 2015
- Changed by Frank Nicholas on 05 Mar 2015
- Changed by Tosso Leeb on 11 Mar 2015