Genetic Testing Could Help Doctors Make Alport Syndrome Diagnosis, Study Reports

Genetic testing of patients with symptoms suggesting Alport syndrome could help doctors make a definitive diagnosis, a study reports.

The tests could also identify genetic errors associated with the disease, helping doctors and patients manage it better.

Researchers published their study in the Journal of Medical Genetics. It was titled “Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations.”

People with Alport syndrome experience progressive loss of kidney function, the result of errors in certain genes, including Col4a3, Col4a4 and Col4a5. The mutations cause abnormalities in a protein known as type IV collagen that plays an important role in kidney structures called glomeruli. It is in these structures that the blood, arriving in the kidney through small vessels called capillaries, is filtered.

A team of researchers developed a diagnostic test capable of identifying 37 alterations in genes, including those associated with Alport syndrome.

They used the test on 302 patients whom doctors thought might have steroid-resistant nephrotic syndrome, a condition characterized by impaired kidney function. Diagnosing SRNS often requires a renal biopsy, an invasive procedure in which a small piece of kidney is removed for doctors to examine.

Tests suggested that 267 patients had nephrotic syndrome and 35 Alport syndrome. They also showed that a faulty gene was the likely cause of 24 percent of the 302 patients’ disease. A likely genetic cause was identified in 21 percent of adults and 20 percent of children suspected of having nephrotic syndrome. In contrast, genetics were the likely cause of 48 percent, or almost half, of those suspected of having Alport syndrome.

Researchers confirmed a genetic cause of disease in 71 patients. Thirty-two had gene mutations that had never been associated with a disease, the team said. These included two deletions in the Nphs1 and Nphs2 genes.

The testing provided a genetic diagnosis “in a significant number of patients” suspected of having nephrotic syndrome or ALS, researchers wrote. Testing “should be undertaken at an early stage of the care pathway” and be able to detect DNA copy variations, they contended.

“Use of clinical genetic testing after diagnosis of SRNS has the potential to stratify patients” and help them manage their disease, the team concluded.