MEDICINE / KIDNEY RESEARCH : Gene Linked to Inherited Disease Isolated

Utah researchers have isolated the gene responsible for a form of inherited kidney disease called Alport syndrome, they report today in the journal Science.

The debilitating disease, which affects about one person in 5,000, leads to loss of the kidney, necessitating dialysis or a kidney transplant. The discovery of the defective gene will quickly lead to genetic counseling for members of families carrying it, experts said, and may lead to the development of new therapies.

Although the syndrome accounts for only about 2% of the 100,000 people in the United States who undergo kidney dialysis, isolation of the gene may provide clues to the causes of other types of hereditary kidney disease.

“The important thing is it’s very likely many other patients with progressive renal disease will have similar types of abnormalities,” said Gary Striker of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md.

“This is a major breakthrough for studying hereditary diseases of the kidney,” added nephrologist Saulo Klahr of Washington University in St. Louis, president of the National Kidney Foundation.

About 160,000 Americans suffer from end-stage kidney failure, and the annual cost of their care totals about $4.4 billion. Although infection, injury, alcohol abuse, diabetes and high blood pressure can cause kidney failure, as many as half of all cases are thought to be genetically linked.

Researchers have discovered the approximate location of the gene that causes a more common form of inherited kidney malady called polycystic kidney disease but have not isolated the gene itself. Today’s Utah report represents the first clear indication of the cause of any form of kidney disease.

The symptoms of Alport syndrome include blood in the urine, progressive kidney failure and, in some cases, hearing loss. The age at which the kidneys fail varies greatly from family to family. In addition, the syndrome may include malformation of the lenses of the eye and abnormalities of blood platelets and white cells.

Although the disorder can affect either sex, males are more likely to suffer severe symptoms.

The researchers at the University of Utah, headed by geneticist David F. Barker and biochemist Curt L. Atkin, have been studying 18 large families with a history of the syndrome.

In three of the families, they have found large defects in a specific gene. That gene is the blueprint for a protein, called type IV collagen, that is a key component of a thin tissue called the glomerular basement membrane. The membrane is used by the kidney to filter blood. It allows metabolic wastes to pass from the blood to the kidney while keeping vital salts and proteins in the bloodstream.

In Alport syndrome patients, the collagen defect causes the slow deterioration of the membrane. As it deteriorates, the membrane frays and eventually scars, causing the kidney to slowly shut down.

Barker believes that the other 15 families being studied have less-severe defects in the same gene that have not been observed in the “rather crude” method of detection. Researchers are using more sophisticated techniques to find defects in the gene in those families.

Barker also hopes to insert the defective gene in mice to create the first animal model of Alport syndrome. Availability of such a model would enable researchers to test new therapies suggested by discovery of the gene.

Eventually, he said, it may be possible to put a healthy form of the gene in the patients to cure the disease.