In other species: Japanese macaque , dog , domestic cat

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: Probably autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2024

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

Molecular basis: Christen et al. (2024) "the genome of the affected [lionhead dwarf] rabbit was sequenced and examined for private variants in NCL candidate genes. The analysis revealed a homozygous ~10.7 kb genomic duplication on chromosome 15 comprising parts of the MFSD8 gene, NC_013683.1:g.103,727,963_103,738,667dup. The duplication harbors two internal protein coding exons and is predicted to introduce a premature stop codon into the transcript, truncating ~50% of the wild-type MFSD8 open reading frame encoding the major facilitator superfamily domain containing protein 8, XP_002717309.2:p.(Glu235Leufs*23)."

Clinical features: Böttcher-Künneke et al. (2020) reported a 2 year old female lionhead dwarf rabbit which "was presented due to behavioural changes, acute anxiety, hyperaesthesia, disorientation, ataxia, loss of vision, phantom scratching, epileptic seizures and a severe nasal dermatitis; all of which progressed within the following twelve months. ... Due to the progressive deterioration of its clinical signs and poor quality of life, the rabbit was euthanised."

Pathology: Böttcher-Künneke et al. (2020) report pathological findings in the affected lionhead dwarf rabbit: "At necropsy, a symmetrical internal hydrocephalus of the lateral ventricles was present. Histologically, neurons of the cerebrum, hippocampus, cerebellum, brain stem and spinal cord were enlarged due to the accumulation of an eosinophilic, partially granular intracytoplasmic material, which led to the diagnosis of a neuronal storage disease." Christen et al. (2024) report additional pathological findings: "Cytoplasmic pigment present in neurons was weakly positive with Sudan black B and autofluorescent. Immunohistology revealed astrogliosis, microgliosis and axonal degeneration."

Breed: Lionhead Dwarf.
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: