Leigh Syndrome, NDUFS7-linked

Gene: NDUFS7

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, NDUFS7 gene; c.535G>A, p.(Val179Met), exon1,  chromosome 20.

Breed: Jack-Chi (Jack-Russell Terrier by Chihuahua hybrid cross)

Medical system: Neurologic

Age of onset of symptoms: 4 months.

Leigh Syndrome describes a neurologic disorder caused by a genetic lesion affecting mitochondrial metabolism. Two puppies from a Jack-Russell Terrier by Chihuahua (Jack-Chi) cross showed clinical signs of a progressive, cerebellar ataxia, intention tremors and involuntary muscle contractions (dystonia), and were diagnosed with Leigh Syndrome. Post-mortem histological examination mortem revealed encephalomalacia with necrosis in brain tissues and accumulation of mitochondria in muscles.  DNA analysis of the affected puppies identified a homozygous mutation within the NDUFS7 gene, which encodes a protein enzyme important in the mitochondrial electron transport chain.  Mutations of this gene are a known cause of Leigh Syndrome in humans.  Further DNA analysis showed that the healthy parents of the affected puppies were both heterozygous carriers for the mutation.  In addition, 50 purebred Jack Russell Terriers and 39 purebred Chihuahuas tested negative for the mutation, as did 1479 control dog genomes from various breeds examined.   Further DNA testing of Jack-Chi animals is now warranted to evaluate the extent of the NDUFS7 mutation within this hybrid breed.

For other examples of Leigh Syndrome in dogs, see:

SLC19A3 gene, Alaskan Husky, Yorkshire Terrier.  OMIA link: [1097]

References:

OMIA link: [2840-9615]

Christen M, Gregor A, Gutierrez-Quintana R, et al. (2024) NDUFS7 variant in dogs with Leigh syndrome and its functional validation in a Drosophila melanogaster model. Sci Rep 14:2975. [pm/38316835]

Cocostîrc V, Paștiu AI, Pusta DL. (2023) An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568.  [pm/38003185]

Contributed by: Arianne Desautels, Coralie L’Eriger and Catherine Sévigny, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)