Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614831 (trait) , 604473 (gene) , 617691 (trait)

Links to relevant human diseases in MONDO:

• MONDO:0013905: autosomal recessive spinocerebellar ataxia 13

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Bandera's neonatal ataxia

Species-specific symbol: BNAt

Species-specific description: Ataxia is characterized by uncoordinated movements and represents a relatively non-specific clinical sign. This entry describes an ataxia form that is caused by a genetic variant in the GRM1 gene. Phenotypically related ataxias in dogs may also be caused by variants in the ATP1B2, CAPN1, ITPR1, KCNJ10, RAB24, SEL1L, SNX14, and SPTBN2 genes. Thus locus heterogeneity for this phenotype must be considered. The GRM1 associated canine disorder represents a model for spinocerebeallar ataxia, autosomal recessive 13 in humans (see MIM link above).

Mapping: By conducting a case-control GWAS on 12 affected and 12 control Coton de Tulear dogs, each genotyped with the Illumina "CanineHD Whole-genome genotyping kit", Zeng et al. (2011) mapped this disorder to a region on chromosome CFA1. Subsequent homozygosity mapping narrowed the region to "a 713 kb region that contained part or all of 4 annotated genes: FBXO30, SHPRH, GRM1, and RAB32".

Molecular basis: Sequencing of the GRM1 positional candidate gene by Zeng et al. (2011) identified the causal mutation as "a 62-bp truncated retrotransposon insert in exon 8".

Clinical features: "Neurologic examination" ... of 7 affected puppies ... "revealed normal mental status, head titubation, intention tremors, and severe gait, stance, and ocular ataxia beginning at 2 weeks of age. One of the pups was able to walk with assistance, but most of the affected pups were unable to stand and used propulsive movements (‘‘swimming’’) for goal-oriented activities. They frequently would fall to lateral recumbency with subsequent decerebellate posturing and paddling. Ocular motor abnormalities included fine vertical tremors at rest and saccadic dysmetria. The condition was nonprogressive at least until 4 months of age." (Coates et al. 2002)

Pathology: "Routine light microscopic and immunocytochemical examination of brain, spinal cord, peripheral nerve, and muscle did not disclose any gross or histologic lesions. Compared with the cerebellum from an age-matched normal dog, the cerebellum from an affected dog showed synaptic abnormalities, including loss of presynaptic terminals and organelles associated with parallel fiber varicosities within the molecular layer and increased numbers of lamellar bodies in Purkinje cells." (Coates et al. 2002)

Breed: Coton de Tulear (Dog) (VBO_0200389).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: