In other species: pig , rabbit

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 312080 (trait) , 300401 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 1990

Species-specific name: Shaking pup

Species-specific symbol: SHP

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in humans, mice and rats), Nadon et al. (1990) reported the causative mutation as "a point mutation at position 219 of the coding sequence [of the PLP gene; now called PLP1] that results in a histidine to proline change in the protein". According to the current variant nomenclature as of 2013 this corresponds to a c.110A>C or p.H37P missense variant.

Clinical features: Affected dogs may be smaller than littermates, and often present with difficulty standing, ataxia, and generalised tremors that typically appear at 10-12 days of age (Griffiths et al., 1981). Death often occurs at 3-4 months of age (Griffiths et al., 1981; Nadon et al., 1990). IT thanks DVM student Judith Browne, who provided the basis of this contribution in May 2023.

Pathology: This disease is characterised by hypomyelination and reduced numbers of mature oligodendrocytes in the central nervous system (CNS) only, with abnormalities most pronounced in the cerebrum and optic nerve (Griffiths et al., 1981; Duncan et al., 1983). Histological features include shortened internodes, reduced thickness or absence of myelin sheaths of CNS axons, and expansion of the perinuclear sheaths and rough endoplasmic reticulum (RER) of oligodendrocytes (Griffiths et al., 1981; Duncan et al.,1983). Due to the X-linked mode of inheritance this disease affects males predominately. Due to X-inactivation in females, animals that are heterozygotes can present with tremors that disappear over time, and can present with myelin mosaicism in the CNS (Duncan et al., 1987). IT thanks DVM student Judith Browne, who provided the basis of this contribution in May 2023.

Breed: Springer Spaniel (Dog) (VBO_0201287).
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: