Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 614725 (gene) , 614739 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Species-specific name: Canine multiple system degeneration; striatonigral and cerebello-olivary degeneration; hereditary cerebellar neuronal abiotrophy

Species-specific symbol: CMSD

Mapping: O'Brien et al. (2005) mapped this disorder to a 15Mb region of chromosome CFA1

Molecular basis: Stee et al. 2023: "This disease has been associated [in a non-peer reviewed conference proceeding] with 2 distinct breed-specific autosomal recessive variants in SERAC1, respectively a nonsense variant (XM_038654522.1:c.1536G>A (p.[Trp512*])) in the Kerry Blue Terrier and a 4-bp deletion (XM_038654522.1:c.182+1_182+4del) in the Chinese Crested [Guo et al., 2013]."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Stee et al. 2023: "This disease has an onset of signs between 9 weeks and 6 months of age. Dogs initially present a mild intention tremor and stiffness in thoracic limb gait, which progresses within 3 to 4 months to severe hypermetric ataxia, spasticity, truncal sway, wide-based stance, delayed postural reactions, and decreased menace response [de Lahunta and Averill, 1976; Deforest et al., 1978; Montgomery and Storts, 1983; O'Brien et al. 2005; de Lahunta et al., 2021]. Signs progress to akinesia, inability to stand and euthanasia by 1 to 2 years of age. Cerebellar atrophy and T2W hyperintensity at the level of the caudate nuclei, putamen, and substantia nigra are visible on MRI in dogs affected for several weeks [O'Brien et al., 2005; de Lahunta et al., 2021]."

Pathology: Stee et al. 2023: "Macroscopic changes in advanced cases include a decreased cerebellar size (6%-9% of total brain weight) and necrosis of the caudate nuclei, putamen, and substantia nigra. Microscopically, an ischemic degeneration of Purkinje cells is seen first, followed by Purkinje cell and secondary granule cell loss. With chronicity, degeneration occurs in the olivary nuclei, followed by acute bilateral degeneration of caudate nuclei and substantia nigra neurons [de Lahunta and Averill, 1976; Deforest et al., 1978; Montgomery and Storts, 1983; O'Brien et al. 2005; de Lahunta et al., 2021]."

Breeds: Chinese Crested (Dog) (VBO_0200345), Ibizan Hound (Dog) (VBO_0200688), Kerry Blue Terrier (Dog) (VBO_0200764).
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: