In other species: domestic cat , horse , taurine cattle , goat , sheep , Magellanic penguin

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600224 (trait)

Single-gene trait/disorder: unknown

Disease-related: yes

Cross-species summary: Also known as neonatal cerebellar cortical degeneration (NCCD)

Species-specific name: cerebellar ataxia

Species-specific description: Cerebellar abiotrophy (CA) has been diagnosed in many dog breeds and different names have been used for the disease - please see separate entries in OMIA for CA diseases with known likely causal variants, e.g. OMIA:002092-9615 : Ataxia, spinocerebellar, SPTBN2-related in Canis lupus familiaris; OMIA:002602-9615 : Cerebellar abiotrophy, VMP1-related in Canis lupus familiaris

Inheritance: Wade et al. (2022): "Based on past breeding studies, pedigree analysis and segregation analysis, CA has been suspected or confirmed to have an autosomal recessive mode of inheritance in many of the affected dog breeds ... ."

Mapping: A GWAS conducted by Shearman et al. (2011) on 11 affected and 19 normal Australian Kelpies, each genotyped with the Affymetrix Canine SNP array v2, failed to reveal any significant associations. A homozygosity analysis of the same data was more revealing, enabling Shearman et al. (2011) to map this disorder to a 3Mb region on chromosome CFA3. The disorder in Beagles, whose causal mutation was described by Forman et al. (2012; see OMIA:002092-9615 : Ataxia, spinocerebellar, SPTBN2-related in Canis lupus familiaris), maps to chromosome CFA18. Wade et al. (2022): “Investigation of clinical and pathological features [in Australian working kelpie dogs] indicated two closely related diseases with differences in age of onset. … A genome-wide association study on 45 CA affected and 290 normal healthy Kelpies identified two significantly associated loci, one on CFA9 and a second on CFA20. Dogs homozygous for the risk haplotype on CFA20 (23 dogs) show clinical signs before ten weeks of age. Missense variants in the sixth exon of disruptor of telomeric silencing 1-like (DOT1Lp.R200Q) and in the only exon of Leucine Rich Repeat And Ig Domain Containing 3 (LINGO3p.R359C), both on CFA20, segregate with the associated risk marker which has incomplete penetrance (42%). Affected dogs homozygous for the risk haplotype on CFA9 have later onset ataxia. A missense variant in exon 5 of Vacuole Membrane Protein 1 (VMP1 p.P160Q) on CFA9 segregates as a fully penetrant Mendelian recessive with later-onset CA.” See 'OMIA:002602-9615 : Cerebellar abiotrophy, VMP1-related in Canis lupus familiaris' for information relating to the VMP1 variant.

Breeds: Australian Kelpie (Dog) (VBO_0200090), Beagle (Dog) (VBO_0200131), Border Collie (Dog) (VBO_0200193), Boxer (Dog) (VBO_0200210), Brittany Spaniel (Dog) (VBO_0200239), English Bulldog (Dog) (VBO_0200485), Kerry Blue Terrier (Dog) (VBO_0200764), Labrador Retriever (Dog) (VBO_0200800), Lagotto Romagnolo (Dog) (VBO_0200804), Working Kelpie (Dog) (VBO_0201434).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).