Researchers Locate Retinitis Pigmentosa Gene : Discovery Opens Way to Prenatal Screening for Some Cases of Blinding Ailment

Times Science Writer

Researchers from Texas and Ireland said Monday that they have identified the location of the gene that causes one major form of retinitis pigmentosa, a condition that has produced blindness in nearly 100,000 Americans and 1.5 million people worldwide.

The discovery of a genetic marker for the disorder, commonly called RP, on Chromosome 3 makes possible prenatal screening for the disorder in some families. It also brings researchers close to isolating the gene.

Finding that gene is particularly important because researchers at present have no idea how the disease develops and no therapy is available.

The discovery is “a major advance,” said Gerald J. Chader of the National Eye Institute in Bethesda, Md.


“This really provides a foot in the door so that researchers can now begin the real task of finding out what that mutant gene is doing, what protein it is coding for,” added cell biologist Matthew LaVail of UC San Francisco.

That knowledge about the biochemistry of the disease should, in turn, allow researchers to develop the first therapy for the disease.

RP occurs when the light-sensitive photoreceptor cells in the retina of the eye degenerate. It is most often diagnosed in childhood when the first symptom, night blindness, appears. As the patient ages, he or she develops “tunnel vision,” a reduction in vision around the edges of the visual field. Generally, the patient eventually becomes completely blind.

Each year, more than 1,500 new cases of RP are diagnosed in the United States.


Researchers have long known that the disease is genetic and have searched for clues to it in families with large numbers of afflicted individuals. In 1985, British researchers announced that they had found a marker for one form of RP on the X chromosome, one of the two human chromosomes that control sex.

But that marker was located quite far from the actual gene, and the researchers have since made little progress in isolating the gene.

In contrast, the new marker is “standing dead on top of the gene” and researchers should have little trouble now in isolating the gene, said medical geneticist Stephen Daiger of the University of Texas Health Sciences Center in Houston.

Daiger and molecular geneticist Peter Humphries of Trinity College in Dublin, Ireland, announced the discovery in a New York City press conference sponsored by the RP Foundation Fighting Blindness.


Humphries and Daiger studied a family which has 100 living members within a 60-mile radius of Dublin. Half of the family members have autosomal dominant RP, which accounts for about 20% of all cases of RP. When one parent in a family has this form, each child has a 50% chance of developing the disease.

Humphries and Daiger compared genetic information--contained in deoxyribonucleic acid, or DNA--from afflicted family members to that from family members who do not have the disorder.

After studying more than half of the 46 human chromosomes, they found that all the afflicted members had a segment of DNA on Chromosome 3 that differed slightly from the same segment in the all other family members. “The marker is a random piece of DNA quite fortuitously linked to the gene, but it is not part of the RP gene,” Humphries said in a telephone interview.

Identification of the marker will allow researchers to conduct prenatal screening for RP among the family members. It should also now be a relatively straightforward process, using standard techniques, to examine DNA adjacent to the marker and identify the gene.


Unfortunately, not all families with autosomal dominant RP have the same defect, Daiger said. He and UCLA ophthalmologist John Heckenlively are studying an American family in Kentucky and Virginia in which 200 of the 600 family members have the disorder. Tentative results, Daiger said, indicate that this family does not have the newly identified marker, suggesting that there is more than one cause of RP.