New Gene Mutation Identified that Causes Alport Syndrome

Researchers from Japan have identified a new mutation in the COL4A5  gene that causes Alport syndrome. The mutation, discovered in a 2-year-old Japanese girl and her mother by Dr. Kazuo Itabash and his team at Showa University School of Medicine, may help diagnose Alport syndrome in other patients.

The study, “A Novel Mutation in a Japanese Family with X-linked Alport Syndrome,” was published in the journal Internal Medicine.

The girl and her mother had a history of proteinuria (abnormal protein in the urine) and hematuria (blood in the urine) but no kidney dysfunction, deafness, or eye problems, which are all common symptoms of the inherited disease.

Through genetic testing the researchers found that the mother and daughter both carried a mutation in exon 32 of the COL4A5 gene, located on the X chromosome. The point mutation occurred where the letter G in their DNA was substituted with the letter C. The substitution may cause type 4 collagen protein to misfold and not function properly. Type 4 collagen is part of the structures that are present in all tissues, including the kidney, inner ear, and eye.

More than 700 disease-causing mutations are reported in the COL4A5 gene and in men with X-linked Alport syndrome. The severity of the condition can be predicted by where the mutation is located on the gene.

Although there is currently no cure for Alport syndrome, early intervention with drugs that inhibit the angiotensin-converting enzyme (ACE) can significantly delay the progression of the disease toward end-stage renal disease. Treatment with angiotensin 2 receptor blockers (ARB) can also inhibit disease progression.

According to the case report, the authors recommend that patients with X-linked Alport syndrome should be treated with ACE inhibitors or ARB in case of microalbuminuria (increased albumin in the urine), proteinuria, or high blood pressure.

“The identification of mutations and characteristic pathological findings were useful in making the diagnosis of [Alport syndrome]. For a close long-term follow-up, the early detection and treatment of women with X-linked [Alport] are important,” the study’s authors wrote.