OMIA:001867-9615 : Lissencephaly and cerebellar hypoplasia, RELN-related in Canis lupus familiaris (dog) |
In other species: sheep
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 257320 (trait) , 600514 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Probably autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2023
Cross-species summary: Renamed from 'Lissencephaly and cerebellar hypoplasia' to 'Lissencephaly and cerebellar hypoplasia, RELN-related' [22/09/2023]
Species-specific name: Cerebellar hypoplasia
Species-specific description: References to other forms of lissencephaly were previously listed here but have been moved to OMIA:002771-9615 : Lissencephaly, generic in Canis lupus familiaris [22/09/2023]
Molecular basis: Littlejohn et al. (2023) "describe a genetic investigation of cerebellar hypoplasia in White Swiss Shepherd dogs, where two affected puppies were identified from a litter with a recent common ancestor on both sides of their pedigree. Whole genome sequencing was conducted for 10 dogs in this family ... [and identified] a frameshift-deletion of the Reelin (RELN) gene (p.Val947*)."
Genetic engineering:
Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Littlejohn et al. (2023): Two affected White Swiss Shepherd "puppies were born clinically normal ... . Both [cerebellar hypoplasia] CH-affected puppies failed to gain weight and developed progressive ataxia from around 2 weeks of age. The puppies had difficulty standing, could not walk in a straight line, had a good suckle reflex but had difficulty latching on to the teat. The puppies had no spontaneous or positional nystagmus, had a normal pupillary light reflex, lacked a menace reflex (normal for age) and segmental spinal reflexes were intact. ... the puppies were euthanised at 4 weeks of age ... ."
Pathology: Littlejohn et al. (2023): "Autopsy [of two affected White Swiss Shepherd puppies] revealed anatomical abnormalities in the brains of both affected puppies, with both animals showing severe CH with lissencephaly ... and moderate internal hydrocephalus with distended lateral and fourth ventricles. ... In both puppies the cerebellum lacked cerebellar folia. ... Microscopically, the normal layered structure ... of the cerebellum was disorganised ... and the molecular and granular layers were thin, with the granular layer of irregular thickness ... and often forming islands of cells ... . Purkinje cells were scattered throughout all layers ... . Vascular structures were prominent. The cerebrum lacked sulci and gyri (agyria) and the white matter was thinned. The cerebral cortex was disorganised with increased thickness of the cortical laminae and neuronal cell bodies that were not vertically aligned."
Breed:
White Swiss Shepherd Dog (Dog) (VBO_0201423).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| RELN | reelin | Canis lupus familiaris | 18 | NC_051822.1 (16579791..17064382) | RELN | 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.
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1580 | White Swiss Shepherd Dog (Dog) | Lissenecephaly and cerebellar hypoplasia | RELN | deletion, small (<=20) | Naturally occurring variant | UU_Cfam_GSD_1.0 | 18 | g.16909944del | c.2839del | p.(V947*) | XM_038562771.1; XP_038418699.1; reported as g.16909942TG>T - information in this table has been updated to reflect HGVS nomenclature. | 2023 | 37334487 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001867-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
Reference
| 2023 | Littlejohn, M.D., Sneddon, N., Dittmer, K., Keehan, M., Stephen, M., Drögemüller, M., Garrick, D. : |
| A frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs. Anim Genet , 2023. Pubmed reference: 37334487. DOI: 10.1111/age.13336. |
Edit History
- Created by Frank Nicholas on 16 Aug 2013
- Changed by Imke Tammen2 on 20 Jun 2023
- Changed by Imke Tammen2 on 22 Sep 2023