In other species: Japanese macaque , domestic cat , rabbit

Categories: Lysosomal storage disease , Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610951 (trait) , 611124 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0012588: neuronal ceroid lipofuscinosis 7

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: One of several variants of neuronal ceroid lipofuscinosis (NCL) or Batten disease: CLN7; NCL7

Molecular basis: Small deletion: "c.843delT is predicted to cause a frame shift and premature stop codon resulting in a truncated protein, MFSD8:p.F282Lfs13*, missing its 239 C-terminal amino acids" in the Chinese Crested breed (Guo et al., 2015). Faller et al. (2016) demonstrated that the same genetic variant is also present in Chihuahuas with neuronal ceroid lipofuscinosis 7. Karli et al. (2016) reported that "the MFSD8:c.843delT variant is also present [and causal] in Chihuahuas without official registrations." Ashwini et al. (2016) also reported the same likely causal mutation in Chihuahuas.

Clinical features: "progressive neurological decline that included blindness, anxiety, and cognitive impairment. A diagnosis of neuronal ceroid lipofuscinosis was made based on neurological signs, magnetic resonance imaging of the brain, and fluorescence microscopic and electron microscopic examination of brain sections" (Guo et al., 2015) Similar clinical signs were also observed in Chihuahuas (Faller et al. 2016).

Pathology: "Both the cerebellum and the cerebral cortex exhibited massive intracellular accumulations of autofluorescent material with a golden yellow emission under blue light illumination . . . . In the cerebellum storage material was most prominent in the Purkinje cells, but substantial amounts of this material were also present in the granular layer . . . . Perinuclear accumulations of autofluorescent storage granules were observed in neurons throughout the cerebral cortex" (Guo et al., 2015) The pathology of affected Chihuahuas was described by Faller et al. (2016).

Prevalence: Pervin et al. (2022) investigated the c.846delT allele in 1007 Chihuahuas in Japan and identified a "carrier rate of 1.29%, indicating a mutant allele frequency (0.00645)".

Breeds: Chihuahua (Dog) (VBO_0200338), Chinese Crested (Dog) (VBO_0200345).
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: