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Primary Congenital Glaucoma (PCG)
| Acronym: | PCG |
| Gene: | LTBP2 |
| Mutation: | c.1449_1452dup |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Primary congenital glaucoma is an inherited eye disorder affecting cats. It belongs to a wider group of disorders, generally known as glaucoma. Glaucomas can be divided into two categories, primary and secondary glaucoma. Primary glaucoma is characterized by its onset without any other ocular cause, while secondary glaucoma appears when another cause is present, which triggers glaucoma. Primary congenital glaucoma (PCG) belongs in the group of primary glaucoma together with primary angle closure glaucoma (PACG) and primary open-angle glaucoma (POAG). PCG is a serious condition that causes irreversible damage to the optic nerve. It is known to affect humans, cats, dogs, and rodents and it is a worldwide leading cause of blindness in humans.
The fluid inside of the eye is called aqueous humor. It is produced behind the iris, in the ciliary body. This fluid flows through the eye and drains from the eye, maintaining normal eye pressure. The drain network in the eye is called the drainage angle or drainage canal. The inadequate outflow of aqueous humor causes a buildup of pressure, and consequently, glaucoma. Prolonged intraocular pressure results in damage to optic nerves, whose damage is irreversible. It can also lead to luxation of the lens and narrowing of the iridocorneal angle.
The Burmese, Siamese, and Persian cats are among the predisposed breeds. Increased intraocular pressure can be identified already by the age of 8 weeks. While the upper normal limit of intraocular pressure is 25 mmHg, glaucoma-affected cats exhibit 40-50 mmHg. PCG is usually bilateral and symmetrical and bilateral moderate enlargement of the globe and corneal edema can be recognized. Examination of affected cats did not detect intraocular inflammation and there were no suggestions of ocular pain.
Gonioscopy is an eye examination of the part of the eye between the cornea and the iris, used for the detection of glaucoma. This examination revealed open iridocorneal angles, with subtle dysplasia of the pectinate ligament, which is in the healthy eye involved in the drainage of the aqueous humor. Other clinical findings, which are visible in cats over 4 months of age or sometimes younger, are prominent and elongated ciliary processes, spherophakia (vision defect characterized by abnormally small and spherical lenses), iris hypoplasia, iris trembling (iridodonesis). Lens instability, anterior or posterior lens subluxation, and luxation appear within the first two years of life. Histological examination of the optic nerve reveals optic nerve head cupping, accompanied by a significant reduction in the number of optic nerve axons.
Primary congenital glaucoma in cats is caused by a mutation in the LTBP2 gene on feline chromosome B3. The mutation includes a 4-basepair insertion, causing a frameshift and expression of a truncated protein. Mutations in the LTBP2 gene have been identified also in human glaucoma patients. Primary congenital glaucoma in cats is inherited in an autosomal recessive pattern. A cat carrying one copy of the mutated gene is heterozygous and will not show the PCG symptoms. When mating two carriers (heterozygotes) at conception each kitten has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Kuehn MH, Lipsett KA, Menotti-Raymond M, Whitmore SS, Scheetz TE, David VA, et al. (2016): A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus). PLoS ONE 11(5): e0154412. doi:10.1371/journal.pone.0154412