Microphthalmia Soft Coated Wheaten Terrier (RBP4)

Acronym:	RBP4
Gene:	RBP4
Mutation:	c.90_92del
Inheritance:	Autosomal recessive with penetrance determined by the maternal genotype
Sample type:	CHS (Cheek Swab), WBE (Whole Blood EDTA)
Method:	Sanger sequencing

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Genetics and characteristics

Microphthalmia Soft Coated Wheaten Terrier type is an inherited disorder of the eyes whose causative mutation has been identified in this dog breed. In humans, microphthalmia is part of a spectrum of congenital eye diseases which are a known cause of childhood blindness. The disorder has been recognized in many dog breeds, however, until now the causative mutation has been confirmed only in Soft Coated Wheaten Terrier dogs. Other breeds affected by microphthalmia include Akita, Australian shepherd, Beagle, Border collie, Borzoi, Cavalier King Charles spaniel, Collie (rough and smooth), Dachshund, Dalmatian, Doberman pinscher, Great Dane, Old English sheepdog, Poodle, miniature, Poodle, standard, Poodle, toy, Portuguese water dog, Saint Bernard, Schnauzer, miniature, Shetland sheepdog, Labrador retriever, Lakeland terrier, Rottweiler, Samoyed, and Tibetan spaniel. Affected dogs have small eyes which seem to be recessed in the eye socket, a condition known as enophthalmos. Also, third eyelids may be prominent. These characteristics are often associated with other eye disorders, such as abnormalities of the cornea, anterior chamber, lens, or retina. Other symptoms may appear, such as clumsy behavior, anxiety, difficulties with coordination, asocial behavior, excessive sleepiness, and partial vision loss.

Microphthalmia Soft Coated Wheaten Terrier (RBP4) is caused by the deletion mutation within the retinol-binding protein gene (RBP4). The role of the RBP4 is to carry vitamin A (retinol) from hepatic stores to peripheral tissues, including the eye, where it participates in the synthesis of retinoic acid. The deficiency of vitamin A during pregnancy is a well-recognized risk factor for ocular birth defects. Mentioned deletion mutation causes decreased vitamin A secretion from hepatocytes to serum. The disorder is inherited in n autosomal recessive pattern with penetrance dependent on maternal genotype. For the disorder to appear in puppies, puppies and mothers must be homozygous for the mutation (affected). The dependence on maternal genotype arises from the obstructed transfer of retinol across the placenta.

 

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Results Reported As

 

 

 

 

 

 

 

 

 

 

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References:

Kaukonen, M., Woods, S., Ahonen, S., Lemberg, S., Hellman, M., Hytönen, M. K., … Lohi, H. (2018). Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease. Cell Reports, 23(9), 2643–2652. doi:10.1016/j.celrep.2018.04.118

Crook A et al. 2011. Canine Inherited Disorders Database (CIDD).