OMIA 001947-9615 : Cerebellar hypoplasia, VLDLR-associated in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 224050

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".

Breed: Eurasier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
VLDLR very low density lipoprotein receptor Canis lupus familiaris 1 NC_006583.3 (91242010..91277030) VLDLR Homologene, Ensembl, NCBI gene

Variants

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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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Eurasier Cerebellar hypoplasia, VLDLR-associated VLDLR deletion, small (<=20) c.1713delC p.W572Gfs*10 2015 25668033

References


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.

Edit History


  • Created by Frank Nicholas on 05 Mar 2015
  • Changed by Frank Nicholas on 05 Mar 2015
  • Changed by Tosso Leeb on 11 Mar 2015