In other species: domestic cat , springbok

Categories: Lysosomal storage disease , Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 268800 (trait) , 606873 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0010006: Sandhoff disease

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: Also known as Sandhoff disease and GM2 gangliosidosis variant 0. A lysosomal storage disease in which there is a buildup (storage) of GM2 gangliosides (a type of glycolipid) in various tissues, due to the lack of the enzyme hexosaminidase, whose task is to break down the GM2 ganglioside into its constituents. Characterised by progressive neuromuscular dysfunction and impaired growth from an early age.

Molecular basis: Rahman et al. (2012) reported the causal mutation in Toy Poodles as being a "single base pair deletion of guanine in exon 3 [of the canine HEXB gene] was identified at nucleotide position 283 of the putative open reading frame (c.283delG). This mutation has the potential to cause a frameshift resulting in the alteration of valine at amino acid position 59 to a stop codon (p.V59fsX)." This is the first published report of a causal mutation for this disorder in dogs. Kolicheski et al. (2017) reported that a likely causal variant in the Shiba Inu breed is "chr2:57,243,656_57,243,658delCCT (CanFam 3.1)". Wang et al. (2018) reported a "3‐base pair deletion in the HEXB gene (c.618‐620delCCT)" as the likely causal variant in an affected Shiba Inu dog.

Prevalence: Kolicheski et al. (2017): "To estimate the frequency of the 3-bp HEXB deletion among the Shiba Inu, all 40 Shiba Inu represented in the University of Missouri DNA repository were genotyped by PCR-RFLP for this deletion. Thirty-seven of the tested Shiba Inu were homozygous for the reference allele; the other 3 were heterozygotes. These heterozygotes were born in 2002, 2004, and 2007. There are no known familial relationships among them or between them and the 2 affected Shiba Inu described here. This observation suggests that the 3-bp HEXB deletion may be rare but widely distributed in the Shiba Inu breed."

Breeds: Golden Retriever (Dog) (VBO_0200610), Mixed Breed (Dog) (VBO_0200902), Poodle, Toy (Dog) (VBO_0201061), Shiba Inu (Dog) (VBO_0201220).
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: