Retinitis pigmentosa is an inherited condition of the retina in which specific photoreceptor cells, called rods, degenerate. The loss of function of these rod cells diminishes a patient's ability to see in dim light and with time can also diminish their peripheral vision. Retinitis pigmentosa is probably caused by mutations in at least ten different genes. Until seven years ago, none of the retinitis pigmentosa genes were known. In 1989, however, researchers in Ireland found that the mutation that caused retinitis pigmentosa in a large Irish family was very near if not within the rhodopsin gene. Soon thereafter, researchers at Harvard identified a specific mutation in the rhodopsin gene that caused retinitis pigmentosa. Our laboratory developed an assay for rhodopsin mutations based on a technique developed by Dr. Sheffield known as "GC-clamped denaturing gradient gel electrophoresis." Using this assay, we have identified over 50 different rhodopsin mutations in our patients.
Retinal appearance of a patient with retinitis pigmentosa caused by a mutation in the rhodopsin gene. The brown pigment in the lower half of the eye is the finding that gives the condition its name. The sharp demarcation between the normal retina above and the abnormal retina below is characteristic of rhodopsin mutations.
In 1991, Harvard scientists identified mutations in the peripherin gene in some patients with retinitis pigmentosa. We applied the denaturing gradient gel technique to this gene and discovered 20 RP families with peripherin mutations. We also used this technique to make the surprising observation that mutations elsewhere in the same gene can cause a macular dystrophy.
Molecular analysis of a family affected with a mutation in the peripherin gene. The pedigree is shown at the top of the gel. Affected individuals are represented by black symbols. All affected patients have the mutation (four bands) while unaffected patients do not (one band). This agreement between the molecular and clinical findings is an important piece of evidence that such mutations actually cause retinal disease.
