Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas


Neuronal Ceroid Lipofuscinoses (NCLs) are inherited neurodegenerative diseases that show progressive declines in the functioning of both cognitive and motor skills. Example of issues that occur include seizures and vision loss and usually greatly shorten the lifespan of species diagnosed with it. Some canine NCL mutations have been identified in an isolated line whereas others have been found to be quite common in an affected breed. It is apparent that this disease does not affect the same gene in every dog breed. Recently, a mutation of MFSD8 which is the gene associated with the CLN7 disease was identified in a Chinese Crested dog with NCL and was also reported in 2 NCL littermate Chihuahuas from Scotland. A study was done to better characterize the NCL phenotype in the Chihuahua breed and to confirm the MFSD8 mutation and the presence of the disease. The scientists also wanted to determine whether mutation is a restriction of a single line of dogs or if the issue is more widespread in the Chihuahua breed.

Four unrelated Chihuahuas from 3 countries (Japan, Italy, and England) which showed similar progressive neurological signs were evaluated for this study. The signs for the Japanese Chihuahuas were; progressive vision loss, anxiety, ataxia (loss of body control), cognitive impairment, and seizures. Both Chihuahuas passed at 23 and 24 months of age. The Chihuahuas from Italy and England showed signs of; loss of house training, severe anxiety, profound loss of learned behaviors, sensitive to loud noises, and severe vision loss are to name a few. Both were euthanized at around 23 months of age. DNA samples were taken from all four. The scientist used the brain histopathology in the Japanese Chihuahua cases. Brain, eye and heart tissue were taken from the Italian Chihuahua shortly after being euthanized. A DNA sample was the only thing obtained from the English dog.

The tissues extracted were examined for the presence of lysosomal storage bodies which is a characteristic on NCL. The histopathological examination of tissue stained the white sections of the cerebellum, cerebral cortex, medulla and meninges. Neurons throughout the brain showed massive perinuclear accumulation of storage bodies which is consistent with the lysosomal storage of the disease. The tissue of the Italian Chihuahua were examined for presence of autofluorescent lysosomal storage. This Chihuahua also exhibited massive accumulations of autofluorescent storage materials in the brain, retina and heart tissue collected.

Results from the DNA samples of all four dogs were found to be homozygous for the MFSD8 single base pair deletion. This is associated with clinical signs and cause of CLN7 NCL. This was the same mutation found in the littermates Chihuahuas from Scotland and the Chinese Crested dog.This suggests that the mutant allele may be common among Chihuahuas given the wide geographic distribution. They also archived 547 unaffected Chihuahuas and 1761 unaffected dogs from 186 different breeds for the MFSD8 allele, but all but the previously discussed Chinese Crested dog were homozygous normal. However, in order to get a better estimation of the frequency of this mutation, Chihuahuas should be screen prior to breeding.

Summary By: Katherine Handley


Akanksha Ashwini, Antonio D'Angelo, Osamu Yamato, Cristina Giordano, Giulia Cagnotti, Tom Harcourt-Brown, Tendai Mhlanga-Mutangadura, Juyuan Guo, Gary S. Johnson, Martin L. Katz,

Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas,

Molecular Genetics and Metabolism,

Volume 118, Issue 4,


Pages 326-332,

ISSN 1096-7192,