Microphthalmia with haematopoietic defects (DNAJC21-related)

Gene: DNAJC21

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: Insertion (SINE element), DNAJC21 gene: c.A155 ins. [A70]AATCCAAGCAGC, p.(52 frameshift STOP 28), exon2, Chr.4.

Medical system: Ocular, blood, teeth

Breed: Portuguese Water Dog

Age of onset of symptoms: Within 2 weeks of age, when eyes open.

A syndrome involving microphthalmia and haematopoietic defects was recently identified in the Portuguese Water Dog.  Ocular symptoms included unilateral or bilateral microphthalmia, with or without cataracts, corneal dystrophy, glaucoma and retinal detachments.  Haematopoietic defects included anemia and decreased platelet numbers (thrombocytopenia).  Dental anomalies were occasionally seen involving enamel hypoplasia, delayed tooth eruption and tooth discoloration.  Affected puppies were notably smaller in size than non-affected littermates.

Twenty-three affected animals were used for a pedigree analysis which showed extensive inbreeding and identified a common ancestor.  Heredity was consistent with an autosomal recessive trait.  Molecular studies were performed on 18 affected animals and identified a SINE element insertion within the DNAJC21 gene.  The DNAJC21 gene codes for a DNA heat shock protein that contributes to ribosome formation and is involved in protein translation, folding and translocation.  A study of 1000 non-affected Portuguese Water Dogs detected 50 carrier (M/N) animals, indicating a penetration of the mutation into the larger breed population with a carrier frequency of 5%.

DNA tests are now available for breeders and veterinarians of the Portuguese Water Dog to help identify carrier animals and eliminate this disease from the breed by selective reproduction.

Note that a SINE insertion in the RAB3GAP1 gene is responsible for a polyneuropathy syndrome seen in the Alaskan Husky that can also involve ocular defects including microphthalmia.

References:

OMIA link: [2847-9615]

Murgiano L, Banjeree E, O’Connor C, et al. (2024) A naturally occurring canine model of syndromic congenital microphthalmia. G3 (Bethesda) 14:jkae067.  [pm/38682429]

With contributions by: Clémence Berguet and Rose Lafortune, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).