Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 270550 (trait) , 604490 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0010041: Charlevoix-Saguenay spastic ataxia

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2023

Cross-species summary: Also called spastic ataxia of the Charlevoix-Saguenay type (SACS, ARSACS)

Mapping: Ekenstedt et al. (2023): "Genome-wide single nucleotide polymorphism (SNP) genotype data was collected from 6 [affected Great Pyrenees] cases and 26 controls, where homozygosity mapping identified a 3.3 Mb region on CFA25 in which all cases were homozygous and all controls were either heterozygous or homozygous for alternate haplotypes."

Molecular basis: Ekenstedt et al. (2023): "Sanger sequencing of the [positional and functional candidate gene] SACS in affected [Great Pyrenees] dogs identified a 4 bp deletion that causes a frame shift and truncates 343 amino acids from the C terminus of the encoded sacsin protein (p.Val4244AlafsTer32)."

Clinical features: Ekenstedt et al. (2023) report disease in Great Pyrenees dogs characterised by "central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. Onset of clinical signs occurred in puppies as young as 4 months of age, with slow progression over several years."

Pathology: Ekenstedt et al. (2023): "Histopathology revealed consistent cerebellar Purkinje cell degeneration, neuronal degeneration in brainstem nuclei, widespread spinal cord white matter degeneration, ganglion cell degeneration, inappropriately thin myelin sheaths or fully demyelinated peripheral nerve fibers, and normal or only mild patterns of denervation atrophy in skeletal muscles."

Breed: Great Pyrenees (Dog) (VBO_0200629).
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: