U-M team: Genetic testing sheds light on degenerative eye disease

February 14, 2007

Genetic testing for eye disease is providing vital information about complex retinal diseases, especially when used to confirm a clinician’s diagnosis.

In a newly published review of such tests that were conducted over a five-year period at the University of Michigan Kellogg Eye Center, scientists were able to confirm a clinician’s diagnosis in half of the cases. The testing took place in the laboratory of Radha Ayyagari, Ph.D., director of Kellogg’s Ophthalmic Molecular Diagnostic Laboratory.

In the February issue of Archives of Ophthalmology, Ayyagari and her colleagues report on 350 genetic tests conducted since 1999, when the U-M Ophthalmic Molecular Diagnostic Laboratory became one of the first laboratories in the nation to receive government approval for ophthalmic testing under the Clinical Laboratory Improvement Amendment (CLIA). For each test described in the current study, scientists analyzed one or more of eight genes known to cause diseases of the retina.

Of the 350 tests, 266 were performed to confirm a clinician’s diagnosis, by far the most common use of genetic testing for eye disease. Another 75 tests sought to determine whether an individual was a “carrier” of a disease, and nine tests were used to predict the likelihood that an individual with a family history of a given eye disease would go on to develop it.

Ayyagari’s team was able to determine the molecular basis of the disease in half of 266 tests conducted to confirm a diagnosis. These results are significant because many retinal diseases present similar symptoms, and it is sometimes difficult for even the most skilled specialist to distinguish one from the other. By comparing a patient’s DNA to known disease-causing genes, scientists deliver information needed to confirm or rule out a diagnosis. To date, scientists have identified over 130 genes associated with retinal disease, such as retinitis pigmentosa and macular degeneration.

The authors observe that genetic testing for eye disease is a relatively new and evolving practice. Says Ayyagari, “Molecular diagnostics does not replace the necessary expertise of the ophthalmologist; rather, it adds a new tool to the ophthalmologist’s diagnostic arsenal.”

The report describes one case in which parents with no family history of retinal degeneration requested genetic testing in hopes of revealing the specific nature of their son’s eye disease. They also wanted to know whether the younger son, who was experiencing more subtle symptoms, had the same disease or a milder vision problem due to a different disease. Testing revealed that both boys had two gene mutations linked to Stargardt’s macular degeneration, a blinding disease that begins in childhood.

Genetic counseling is a crucial part of the genetic testing process, particularly when the patient may face the possibility of blindness, says Ayyagari. The family needs to prepare for all possible test results, understand the implications of test results for the patient and other family members, and be aware of the limitations of genetic testing. If physicians do not have the time or skills to provide this background, Ayyagari urges them to refer their patients to genetic counselors.

The study also reported that a diagnosis could not be confirmed in 133 cases, or half the tests conducted to confirm a diagnosis. “It is very difficult for patients to understand that the test may not be definitive,” says Ayyagari. “Genetic testing may not always yield the firm facts we receive in other kinds of testing, such as blood tests for cholesterol levels.”

A related point of confusion is that an inconclusive result does not necessarily rule out a diagnosis for a given disease. Limitations still exist in technologies for genetic testing, explains Ayyagari. In addition, very slight genetic variations believed to be benign may have either a cumulative effect or may alter the way another gene functions. Finally, while there has been great progress, scientists have yet to identify all the genes that contribute to disease of the retina.

“Tomorrow we may discover a new gene that explains many of the previously inconclusive test reports,” says Ayyagari.

In a related paper in the same issue of Archives of Ophthalmology, Stephen Daiger, Ph.D., University of Texas Health Science Center, writes on the promise of genetic testing for eye disease. He says, “Across all of the categories of inherited retinopathy, careful screening of known disease genes leads to detection of pathogenic mutations in 25% to 90% of patients, an extraordinary accomplishment.”

It is to the patient’s advantage to have a molecular diagnosis on file, observes Ayyagari. “When treatments begin to emerge for these complex genetic diseases,” she says, “the individual’s genotype may determine whether a new treatment will be the one that works for that patient.”

Source: University of Michigan Health System

Explore further: At-home genetic testing leads to misinterpretations of results

Related Stories

At-home genetic testing leads to misinterpretations of results

March 19, 2018
Home genetic tests like AncestryDNA and 23andMe are more popular than ever, with sales topping $99 million in 2017. But a new study led by a Boston University School of Public Health researcher highlights the potential negative ...

Discovery promises improved diagnosis and understanding of endometriosis

March 19, 2018
Feinstein Institute for Medical Research scientists announced an experimental, rapid and non-invasive way to diagnose endometriosis, which may lead to earlier and more effective treatments for this disorder that affects approximately ...

ENDO 18: New model, new drugs, and a 'remarkable' response in adrenal cancer

March 19, 2018
Two University of Colorado Cancer Center studies presented at ENDO 2018 use new models to identify genetic targets and test promising treatments in adrenal cancer. One patient was treated with the immunotherapy pembrolizumab ...

Gene panel predicts course of cystic fibrosis

March 19, 2018
Researchers at National Jewish Health have identified 10 immune-related genes whose activity during a respiratory infection predict the long-term prognosis for cystic fibrosis patients better than conventional measures. Five ...

How allergens trigger asthma attacks

March 19, 2018
A team of Inserm and CNRS researchers from the Institute of Pharmacology and Structural Biology have identified a protein that acts like a sensor detecting allergens in the respiratory tract that are responsible for asthma ...

New methods find undiagnosed genetic diseases in electronic health records

March 15, 2018
Patients diagnosed with heart failure, stroke, infertility and kidney failure could actually be suffering from rare and undiagnosed genetic diseases.

Recommended for you

Gradual release of immunotherapy at site of tumor surgery prevents tumors from returning

March 21, 2018
A new study by Dana-Farber Cancer Institute scientists suggests it may be possible to prevent tumors from recurring and to eradicate metastatic growths by implanting a gel containing immunotherapy during surgical removal ...

Immune cells in the retina can spontaneously regenerate

March 21, 2018
Immune cells called microglia can completely repopulate themselves in the retina after being nearly eliminated, according to a new study in mice from scientists at the National Eye Institute (NEI). The cells also re-establish ...

Cold can activate body's 'good' fat at a cellular level, study finds

March 21, 2018
Lower temperatures can activate the body's 'good' fat formation at a cellular level, a new study led by academics at The University of Nottingham has found.

Switch discovered to convert blood vessels to blood stem cells in embryonic development

March 20, 2018
A switch has been discovered that instructs blood vessel cells to become blood stem cells during embryonic development in mice. Using single-cell technology, researchers from the Wellcome Sanger Institute in Cambridge and ...

Don't blame adolescent social behavior on hormones

March 19, 2018
Reproductive hormones that develop during puberty are not responsible for changes in social behavior that occur during adolescence, according to the results of a newly published study by a University at Buffalo researcher.

Stem cells treat macular degeneration

March 19, 2018
In July 2015, 86-year-old Douglas Waters developed severe age-related macular degeneration (AMD). He struggled to see things clearly, even when up close.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.