MEDICINE / GENETICS : Key Cause of Retinitis Pigmentosa Found

Researchers have identified what they think is the last piece of the genetic puzzle of a major form of retinitis pigmentosa, an inherited disorder that has produced blindness in about 100,000 Americans and 1.5 million people worldwide.

The discovery should make possible prenatal screening for the disorders in families with “autosomal dominant” RP, which accounts for about 43% of all cases of the disorder, said geneticist Jeanette S. Felix, director of science for the National Retinitis Pigmentosa Foundation in Baltimore.

Scientists found a defect in a human gene that is the counterpart of a genetic defect discovered in mice two years ago by UCLA researchers. Its identification, reported last week in the British journal Nature, represents “an important demonstration of the value of animal research in attacking human diseases,” said Felix.

Researchers now believe that they have discovered all the major genetic defects that cause autosomal dominant RP, in which a child who receives the gene from either parent develops the disorder. The remainder of cases require that the child receive a gene from each parent to develop the condition, and researchers have not yet isolated the gene or genes that cause that form.

It is also hoped that identification of the genetic defect will lead to a better understanding of how retinitis pigmentosa develops, and thence to the discovery of a treatment for it. No treatment is available now.

Retinitis pigmentosa, or RP, causes the degeneration of the retina, the cells that line the back of the eye, capture light and transmit signals to the brain for interpretation. The first symptom of RP is usually night blindness, or an inability to see in dimly lit places. That is followed by a reduction in peripheral vision, which leads to tunnel vision and, in many cases, complete blindness.

One out of every 80 people carries a gene for RP.

Researchers had previously found that a defect in the gene for a purple, light-sensitive pigment called rhodopsin is responsible for about 30% of the cases of autosomal dominant RP. They believe that the newly found defect may be responsible for the remaining 70%.

The new genetic defect was identified independently by two groups of researchers: one led by geneticist Peter Humphries of Trinity College in Dublin, Ireland, and the second by geneticists Thaddeus P. Dryja and Eliot L. Berson of the Harvard Medical School.

Humphries and his group studied members of a large, four-generation Irish family with autosomal dominant RP. They found that the gene that caused the disorder in this family was located in a narrow region of chromosome 6, one of the 23 pairs of chromosomes that provide the genetic blueprint for humans. They then found defects in the gene for a protein called peripherin, the same gene that had been identified in mice.

Peripherin is involved in peripheral vision, perhaps helping to stabilize the structure of the outer edges of the retinal disc, Humphries speculated.

Taking a somewhat different approach, Dryja and Berson studied the peripherin gene in hundreds of unrelated patients with RP. They ultimately discovered three different defects in the peripherin gene in three families with autosomal dominant RP.

Although scientists can now perform prenatal screening in families with a known genetic defect, Felix said, they cannot expand the screening to other families until they are confident that the two genes cause virtually all cases of autosomal dominant RP.