Null RPGRIP1 alleles in patients with Leber congenital amaurosis

We isolated and characterized the entire coding sequence of a human gene en coding a protein that interacts with RPGR, a protein that is absent or muta nt in many cases of X-linked retinitis pigmentosa. The newly identified gen e, called "RPGRIP1" for RPGR-interacting protein (MIM 605446), is located w ithin 14q11, and it encodes a protein predicted to contain 1, 259 amino aci ds. Previously published work showed that both proteins, RPGR and RPGRIP1, are present in the ciliary structure that connects the inner and outer segm ents of rod and cone photoreceptors. We surveyed 57 unrelated patients who had Leber congenital amaurosis for mutations in RPGRIP1 and found recessive mutations involving both RPGRIP1 alleles in 3 (6%) patients. The mutations all create premature termination codons and are likely to be null alleles. Patients with RPGRIP1 mutations have a degeneration of both rod and cone p hotoreceptors, and, early in life, they experience a severe loss of central acuity, which leads to nystagmus.