Retrospective Diagnosis of Feline GM2 Gangliosidosis Variant 0 (Sandhoff-Like Disease) in Japan: Possible Spread of the Mutant Allele in the Japanese Domestic Cat Population

Abstract

ABSTRACT. GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal storage disease caused by simultaneous deficiencies of acid β-hexosaminidase (Hex) A and Hex B due to an abnormality of β-subunit, a common component in these enzyme molecules, which is coded by the HEXB gene. In the present study, a retrospective diagnosis was performed in 2 previous suspected cases of feline Sandhoff-like disease using a DNA test to detect the causative mutation identified previously in 4 cats in 2 other families of Japanese domestic cats. Enzymic analysis was also performed using stored leukocytes and plasma collected from the subject families in order to investigate the usefulness of enzymic diagnosis and genotyping of carriers. The DNA test suggested that the 2 cases were homozygous recessive for the mutation. Consequently, 6 cats homozygous for the same mutation have been found in 4 separate locations of Japan, suggesting that this mutant allele may be spread widely in the Japanese domestic cat populations. In enzymic analysis, Hex A and Hex B activities in leukocytes and plasma measured using 4-methylumbelliferyl N-acetyl-β-D-glucosaminide as a substrate were negligible in affected cats, compared with those in normal and carrier cats. However, there was a wide overlap in enzyme activity between normal and carrier cats. Therefore, it was concluded that enzymic analysis is useful for diagnosis of affected cats, but is not acceptable for genotyping of carriers.KEY WORDS: acid β-hexosaminidase A, GM2 gangliosidosis variant 0, Japanese domestic cat, retrospective diagnosis, Sandhoff disease.

Magnetic Resonance Findings of the Corpus Callosum in Canine and Feline Lysosomal Storage Diseases

“…Cases in this study had a mutation in the HEXB gene encoding β-hexosaminidase. Detailed information was reported previously [4], [5].…”

Rapid and Simple Polymerase Chain Reaction—Based Diagnostic Assays for GM2 Gangliosidosis Variant 0 (Sandhoff-Like Disease) in Japanese Domestic Cats

“…In addition, recent reports suggest that this mutant allele is widely spread in the Japanese domestic cat population. 7,17 To the authors' knowledge, 9 affected cats have been diagnosed with Sandhoff-like disease over a wide geographic area from central (Kanto district) to southern (Kyushu district) Japan since the 1990s (O. Yamato, unpublished information, 2009). Therefore, it is likely that a veterinary practitioner will encounter affected cats within Japan and possibly abroad as well.…”

“…ac.jp ulant from 6 wild-type, 5 heterozygous carrier, and 3 affected cats and stored them using Flinders Technology Associates filter paper (FTA card) a from a previous study. 7,8,17 The genotypes had been determined using a direct sequence analysis. 8 Heparinized whole blood samples were also collected from 1,015 mixed breed cats for screening.…”

“…Previously, in the PCR-PIRA-1 assay, a different Taq polymerase was used, and FTA cards were not used. 8,17 The PCR-PIRA-1 assay was combined with FTA cards in the study. In the present study, the PCR-PIRA-1 assay was initially carried out using the previously used Taq polymerase and a pretreated disc of FTA card as a template, but a 91-bp fragment derived from wild-type cats did not completely disappear after digestion with RsaI for unknown reasons (data not shown), and made it impossible to clearly distinguish a wild genotype from a heterozygous genotype.…”

Animal models of GM2 gangliosidosis: utility and limitations

“…42 , 43 This mutation is a single nucleotide substitution resulting in premature termination at codon 223, midway through the β subunit. 44 , 45 Also, a 15 base pair deletion at the 3′ end of intron 11 of HEXB , which included the preferred splice acceptor site, has been identified in European Burmese cats. 46 …”