Kristal Rust

Uveitis in patients with sarcoidosis is not associated with mutations in NOD2 (CARD15)

PURPOSE Mutations in NOD2 are responsible for Blau syndrome, a systemic disease triad involving the uvea, joints, and skin. NOD2 mutations are also associated with Crohn disease. Both Blau syndrome and Crohn disease involve granulomatous inflammation and uveitis, as does sarcoidosis. We sought to determine if NOD2 mutations were present in patients with sarcoidosis, especially those with uveitis. METHODS NOD2 gene exons were sequenced from DNA obtained from sarcoidosis patients. The diagnoses of sarcoidosis and uveitis were verified from clinical records. RESULTS NOD2 polymorphisms were found in 26 patients with sarcoidosis (13 with uveitis). There was no significant difference in allele frequencies between patients with and without uveitis. CONCLUSIONS Despite the strikingly similar pathologies of Blau syndrome and sarcoidosis, no mutations were found to be associated with sarcoidosis in a group of patients, regardless of the presence of uveitis.

Malattia leventinese: refinement of the genetic locus and phenotypic variability in autosomal dominant macular drusen

PURPOSE To study the phenotypic variability in patients inheriting the disease gene for malattia leventinese (dominant macular drusen) and refine the localization of the gene. METHODS A family with dominant radial drusen was ascertained and studied with clinical examination and DNA linkage analysis. Inheritance of the disease gene was determined by DNA analysis and used to document the variability in phenotypic expression. RESULTS Fifty family members were studied with fundus photography and genotyping. Linkage analysis showed that the disease in this family was linked to chromosome 2p16-21 with a maximum lod score of 3.72 at D2S2153. An affected patient with obligate recombinations allowed refinement of the disease interval to a 6.2-cM region between D2S2227 and D2S378. The phenotype of older affected patients varied from severe geographic atrophy or subretinal fibrosis to a single druse adjacent to the optic disk. Small and medium-sized, nonradial, and soft macular drusen seen in four older individuals in the family were not specifically associated with the disease haplotype. CONCLUSIONS Refinement of the localization of the gene for malattia leventinese will facilitate its positional cloning. Genotypic documentation of the variable expression of the disease shows that a single, large, subretinal druse adjacent to the optic disk is consistent with inheritance of the disease gene. Soft macular drusen in low abundance were not specifically associated with inheritance of the disease gene. These results will facilitate the genetic counseling of patients with malattia leventinese. It is unknown what proportion of age-related macular degeneration arises from mutations in disease genes for dominant drusen.

Refining the primary open-angle glaucoma GLC1C region on chromosome 3 by haplotype analysis

The GLC1C locus for primary open‐angle glaucoma (POAG) is inherited as an autosomal dominant trait. This region on chromosome 3 is 11 cM long. DNA samples from members of a Greek and an American GLC1C family were obtained to determine whether additional typing of microsatellite markers in family members might narrow the region. GLC1C family members were evaluated clinically for POAG on the basis of open angles, intraocular pressures, cupping of discs, and visual fields. DNA samples from the Greek and Oregon GLC1C families were used to further refine the GLC1C region using microsatellite markers. A total of 22 affected members were identified in the two families. Common alleles for D3S3637 and D3S3612 were present in the disease haplotype from both families, suggesting that they may have a common founder. A newly diagnosed patient in the American family had a recombination in the distal portion of the GLC1C haplotype. This recombination narrows the GLC1C region from 11 to 4 cM.