18.2.4  Low-Tension Glaucoma

Genetic testing for the OPTN (Optineurin) E50K mutation can be useful in patients with an onset of severe low-tension glaucoma in the third or fourth decade, or in those with a family history of low-tension glaucoma.

18.2.5  Primary Open-Angle Glaucoma

(Adult-Onset)

Mutations in the gene coding for myocilin (MYOC) may be found in up to 3–5% of patients with adultonset primary open angle glaucoma. Mutations are more likely to be found in patients with a strong family history of glaucoma (especially those with siblings as well as an affected parent) and in individuals who are affected somewhat earlier than the typical adult-onset primary open angle glaucoma patient (fourth or fifth decades).

Summary for the Clinician

››Current glaucoma gene testing is most useful for the early onset forms of the disease.

››Patients with anterior segment dysgenesis should be tested for all four genes associated with these syndromes, although clinical features can help prioritize testing.

››Juvenile open angle glaucoma patients with a strong family history should be tested for mutations in MYOC.

››Patients with recessive or sporadic forms of congenital glaucoma should be tested for mutations in CYP1B1, especially if there is a family history of consanguinity.

››Low tension glaucoma patients with a family history could be tested for the OPTN E50K mutation.

››Patients with a strong family history adult-onset primary open angle glaucoma may benefit from MYOC mutation screening.

18.3  How Do I Collect Samples and Where Do I Send Them for Analysis?

Genetic testing typically uses DNA samples purified from white blood cells or from buccal (cheek) cells collected using a mouthwash procedure (swish and spit) (Fig. 18.1) or a buccal swab (Fig. 18.2). A blood sample provides the most of DNA, however, the swish and spit method and buccal swabs can provide sufficient DNA for most genetic tests and frequently are more convenient to obtain from the patient [18]. The lab performing the testing will indicate the best collection procedure for the test they are performing, and they will provide detailed instructions for obtaining the sample.

Once a sample is obtained, the genetic test is performed by a special laboratory equipped to perform the test. Laboratories performing clinical genetic testing must be certified by a state agency according to the Clinical Laboratory Improvement Amendment of 1988 (CLIA). If a lab is not CLIA certified it is not allowed to provide results to the clinician or to the patient. CLIA certified laboratories return test results to the clinician who has ordered the test. It is the responsibility of the clinician to convey the results to the patient and provide the necessary genetic counseling.

There are a number of CLIA certified laboratories that perform genetic testing for the genes listed in this chapter. A current list of laboratories is found at the website GeneTests (www.genetests.org). In addition to the CLIA laboratories listed at GeneTests, there is also a network of CLIA certified laboratories supported by the National Eye Institute (NEI) to perform ocular gene testing for the eyeGENE project. The goal of this project is to develop an accessible database linking genes, genotypes, and phenotypes for over 100 ocular disease genes [19]. Most of the genes discussed in this chapter are included in the eyeGENE panel. More information about eyeGENE can be found at the eyeGENE website (www.nei.nih.gov/resources/eyegene.asp).

Fig. 18.2  The buccal swabs are used to vigorously scrape cheek cells from the buccal membrane for 10 seconds and then are returned to their containers.

Summary for the Clinician

››Genetic testing is performed on a DNA sample from the patient.

››DNA may be prepared from a blood sample or a buccal cell sample (from a mouthwash procedure or buccal swab).

››Genetic tests are performed in a CLIA certified laboratory.

››Genetic test reports are conveyed to the patient through the clinician.

››Laboratories that currently perform glaucoma gene testing may be found at the GeneTests and eyeGENE web sites.

18.4  How Should the Results of Genetic

Testing Be Interpreted for the

Patient’s Use?

Glaucoma gene testing can help patients and their family members understand their risk of disease. In addition to the identification of individuals at risk for the disease, mutation specific clinical outcomes (genotype/phenotype correlations) can direct appropriate treatment.

18.4.1  Genetic Counseling

A major benefit of mutation testing is the identification of individuals at risk for the disease. Affected individuals need to know the risk of transmitting the disease to their offspring and the risk that their siblings or other family members may develop the disease. Unaffected individuals may learn that they are mutation carriers, which can influence their risk of developing the disease and their risk of transmitting the mutation to their offsprings. Physicians, by virtue of their medical training, are qualified to discuss disease risk in the context of mutation testing with their patients; however, trained genetic counselors can also help with this process if necessary. Specific issues of disease risk for the forms of glaucoma that can currently be tested for are discussed below.