A new locus for autosomal dominant cataract on chromosome 19: linkage analyses and screening of candidate genes.

PURPOSE: To map and identify the mutated gene for autosomal dominant cataract (ADC) in family ADC4. METHODS: Ophthalmic evaluations were performed on an American family with ADC and a panel of polymorphic DNA sequence-tagged site (STS) markers for known ADC loci and other genome-wide polymorphic markers were used to map the gene; two-point lod scores were calculated. Fine mapping was undertaken in the chromosomal regions of maximum lod scores, and candidate genes were sequenced. RESULTS: A four-generation American family with ADC was studied. The only phakic individual exhibited white and vacuolated opacities in the cortical region. This ADC locus mapped to several suggestive chromosomal regions. Assuming full penetrance, the highest calculated maximum lod score was 3.91 with D19S903 [corrected] On chromosome 12, we sequenced all exons and the exon-intron borders of the membrane intrinsic protein (MIP) gene. On chromosome 19, all exons and the exon-intron borders of genes for lens intrinsic membrane2 (LIM2), ferritin light chain (FTL), and the human homologue of the Drosophila sine oculis homeobox 5 (SIX5) were sequenced, and the 3' untranslated repeat region (UTR) of the dystrophy (DMPK) gene and both the 5' and 3' UTRs of the SIX5 genes were amplified; the promoter for LIM2 was sequenced. For these genes, the sequence matched that in the reference libraries, and the DMPK gene had a normal number of CTG repeats. CONCLUSIONS: The mutated gene in ADC4 probably represents a new, not yet identified locus on chromosome 19. In one phakic member, the cortical cataracts were punctate and vacuolated.

Multifocal electroretinography evaluation for early detection of retinal dysfunction in patients taking hydroxychloroquine.

PURPOSE: To evaluate macular function using multifocal electroretinography (mfERG) in a cohort of asymptomatic patients taking hydroxychloroquine and a patient with maculopathy secondary to hydroxychloroquine treatment. METHODS: mfERG recordings were obtained for both eyes of 11 patients taking hydroxychloroquine without clinical signs of toxicity and 1 patient with toxic maculopathy. Initially, the classic m-sequence paradigm for the first-order kernel (103 hexagons; 2.7 candela x seconds/m2 peak luminance) was recorded. After that, another special stimulation mode was applied, which emphasized second-order adaptational effects (modulated multifocal flashes with interleaved global flashes, MF0F0 paradigm). RESULTS: The patient with toxic maculopathy and one patient without toxicity had multiple areas of decreased retinal responses bilaterally (classic m-sequence). The patient with toxicity and another three patients without toxicity presented with multiple areas of decreased retinal function in both eyes with the second-order component of the MF0F0 paradigm. Repeated recordings of 1 patient 8 months after the initial recording demonstrated evidence for reproducibility of the second-order adaptive effects. CONCLUSION: Clinically asymptomatic patients receiving hydroxychloroquine treatment can have substantial local decreases in their retinal function, as reflected by the changes in mfERG recordings, possibly indicating a preclinical stage of drug-related toxicity.