Characteristics of the test: (includes 1 gene)

CYP1B1 (OMIM #601771)

Basic characteristics of the clinical phenotype
Glaucoma includes a group of diseases in which there is a persistently elevated intraocular pressure (IOP), which irreversibly damages the optic nerve and leads to progressive damage to central and peripheral vision. Left untreated, glaucoma leads to complete loss of visual function and absolute blindness. Glaucoma in children is divided into congenital and secondary.

Congenital glaucoma (PCG, OMIM #231300) is a disease in which intraocular pressure is permanently elevated from birth due to impaired outflow of intraocular fluid. The incidence of congenital glaucoma varies between 1:1250 to 1:20000 depending on geographic location and ethnic group. The disease is most common in the Slovak Roma population (1:1250), followed by Saudi Arabia (1:2500), South India (1:3300) and Western nations (1:5000-22000). Congenital glaucoma is the most common cause of total blindness in children.

Increased IOP leads to permanent and irreversible damage to the optic fibers and thus to a progressive reduction of visual functions. In 60% of children, congenital glaucoma manifests itself by the 6th month after birth, and in 80% by the end of the first year. The first symptoms are photophobia, large eyes, lacrimation, clouding of the corneas.

Juvenile glaucoma is considered a later-onset congenital glaucoma. The onset of the disease is adolescence. The clinical picture of juvenile glaucoma is much milder than that of congenital glaucoma.

Open- and closed-angle glaucoma are rare before the age of 40, and the incidence increases gradually with age (due to the aging of the population in developed countries, a further increase in incidence is expected).

Secondary glaucoma includes a group of diseases in which increased IOP is due to inflammation due to trauma, an intraocular tumor, or another cause.

The most common cause of congenital glaucoma is mutations in the CYP1B1 gene, with inheritance being autosomal recessive. Over 150 pathogenic variants leading to congenital glaucoma have been identified in the CYP1B1 gene to date.

Reasons for referring:
Candidates for this test are all patients with symptoms of primary congenital, juvenile, open- and angle-closure glaucoma, as well as relatives of patients in whom the mutation is known.

Interpretation of results:
· The detection of point mutations and small deletions/insertions in the CYP1B1 gene will allow a genetic diagnosis of Congenital Glaucoma.
· Presence of large deletions and insertions cannot be detected by this method. A combination with a suitable CNV analysis (MLPA, aCGH) is recommended for their detection.
· The genetic counselor will interpret and answer all questions about your result.

Method: Sanger sequencing.

The method involves bi-directional DNA sequencing of all coding exons and intron-exon boundaries of the CYP1B1 gene. The laboratory offers single exon or exon pair sequencing in relatives of the patients to determine the carrier status in cases where the mutation is known (Test #182).

Sensitivity of the method: 99.5%

What does the test involve?
· DNA isolation and sample storage.
· Direct sequencing of target genes/gene regions to detect pathogenic mutations.
· Forming a written result of the genetic test.
· Diagnostic interpretation of results and genetic counseling.

Biological material: Venous blood or DNA

For more information, please read the "Biological material requirements and shipping information" carefully.