Diffuse loss of sensitivity in early glaucoma. (1/64)

PURPOSE: To establish whether there is significant diffuse loss of sensitivity in a population of patients with early glaucoma. METHODS: The differential light sensitivities at the 10 most sensitive locations from within the central 24 degrees of program 30-2 of the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA) were compared in 38 pairs of age-matched subjects, one of each pair with early primary open-angle glaucoma (POAG) and the other with normal eyes. All subjects had had experience with automated perimetry and had clear media, visual acuity of 20/25 or better, and one or fewer false-positive or false-negative responses to catch trials. RESULTS: The mean difference in age between the subjects with glaucoma and normal subjects was 29 days (P = 0.44, maximum 1.42 years). The mean paired difference in pupil size was 0.16 mm (P = 0.26), and visual acuity was higher in the glaucoma-affected subjects (P = 0.044). The 10 highest sensitivity measurements in the POAG-affected subjects were found to be lower by a median of between 1.0 and 2.0 dB than those in the normal pair members (0.0001+info)

Novel locus for autosomal recessive cone-rod dystrophy CORD8 mapping to chromosome 1q12-Q24. (2/64)

PURPOSE: To map the disease locus of a two-generation, consanguineous Pakistani family with autosomal recessive cone-rod dystrophy (arCRD). All affected individuals had night blindness, deterioration of central vision, photophobia, epiphora in bright light, and problems with color distinction. Fundoscopy revealed marked macular degeneration and attenuation of retinal vessels. Mild pigmentary changes were present in the periphery. METHODS: Genomic DNA was amplified across the polymorphic microsatellite poly-CA regions identified by markers. Alleles were assigned to individuals that allowed calculation of LOD scores using the Cyrillic (Cherwell Scientific, Oxford, UK) and MLINK (accessed from ftp://linkage. rockefeller.edu/softeware/linkage/) software programs. The cellular retinoic acid-binding protein 2 (CRABP2), cone transducin alpha-subunit (GNAT2), potassium inwardly rectifying channel, subfamily J, member 10 (KCNJ10), genes were analyzed by heteroduplex analysis and direct sequencing for mutations. RESULTS: A new locus for arCRD (CORD8) has been mapped to chromosome 1q12-q24. A maximum two-point LOD score of 4.22 was obtained with marker D1S2635 at recombination fraction of theta = 0.00. Two critical recombinations in the pedigree positioned this locus to a region flanked by markers D1S457 and D1S2681. A region of homozygosity was observed within the loci D1S442 and D1S2681, giving a probable critical disease interval of 21 cM. Mutation screening of the three candidate genes CRABP2, GNAT2, and KCNJ10 revealed no disease-associated mutations. CONCLUSIONS: The findings therefore suggest that this phenotype maps to a new locus and is due to an as yet uncharacterized gene within the 1q12-q24 chromosomal region.  (+info)

Sensory capacity of the royal college of surgeons rat. (3/64)

PURPOSE: To apply noninvasive tests for examining visual and other sensory functions of pigmented Royal College of Surgeons (RCS) rats compared with pigmented and albino control animals. METHODS: Rats aged 3 and 7 months were tested with a general neurologic examination that assessed visual, auditory, tactile, and whisker displacement responses. Photophobic responses and visual discrimination were also measured. RESULTS: Dystrophic RCS rats failed the visual presentation tests, even at 3 months of age, and showed diminished performance on tactile tests. Auditory and whisker displacement performances were normal. Albino rats also showed diminished performance on the visual test, particularly to stimuli presented in the upper visual field. Photophobic responses were diminished in the dystrophic RCS rats compared with the pigmented control animals. Albino animals showed heightened photophobia. The dystrophic rats failed to reach criterion levels of performance on the visual discrimination test even with gratings of 0.045 cyc/deg. CONCLUSIONS: The tests used discriminate deteriorated complex visual functions in RCS rats at ages when some simple reflexes can still be demonstrated. As such, they provide easily executed tests for screening for the effects of reparative treatments such as transplantation, administration of growth factors, and gene transfer technology. The integrity of whisker and auditory function are important when using tests requiring polysensory inputs. The somatosensory defect is surprising but may be useful in searching for the gene locus of the retinal disorder. The aberrations seen in the albino rats may be attributable to the effects of light damage and unfiltered light.  (+info)

Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. (4/64)

Lymphedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphedema of the limbs, with variable age at onset, and double rows of eyelashes (distichiasis). Other complications may include cardiac defects, cleft palate, extradural cysts, and photophobia, suggesting a defect in a gene with pleiotrophic effects acting during development. We previously reported neonatal lymphedema, similar to that in Turner syndrome, associated with a t(Y;16)(q12;q24.3) translocation. A candidate gene was not found on the Y chromosome, and we directed our efforts toward the chromosome 16 breakpoint. Subsequently, a gene for LD was mapped, by linkage studies, to a 16-cM region at 16q24.3. By FISH, we determined that the translocation breakpoint was within this critical region and further narrowed the breakpoint to a 20-kb interval. Because the translocation did not appear to interrupt a gene, we considered candidate genes in the immediate region that might be inactivated by position effect. In two additional unrelated families with LD, we identified inactivating mutations-a nonsense mutation and a frameshift mutation-in the FOXC2 (MFH-1) gene. FOXC2 is a member of the forkhead/winged-helix family of transcription factors, whose members are involved in diverse developmental pathways. FOXC2 knockout mice display cardiovascular, craniofacial, and vertebral abnormalities similar to those seen in LD syndrome. Our findings show that FOXC2 haploinsufficiency results in LD. FOXC2 represents the second known gene to result in hereditary lymphedema, and LD is only the second hereditary disorder known to be caused by a mutation in a forkhead-family gene.  (+info)

Amniotic membrane transplantation for partial limbal stem cell deficiency. (5/64)

AIM: To examine the efficacy, safety, and long term outcomes of amniotic membrane transplantation for corneal surface reconstruction in cases of partial limbal stem cell deficiency. METHODS: 17 eyes of 15 patients with partial limbal stem cell deficiency underwent superficial keratectomy of the conjunctivalised corneal surface followed by amniotic membrane transplantation. Cases were followed up for at least a year. RESULTS: All eyes exhibited a stable, intact corneal epithelial surface after a mean follow up period of 25.8 months with no eyes developing recurrent erosion or persistent epithelial defect. The mean time to re-epithelialisation was 22.8 days. Overall improvement in visual acuity was observed in 92.9% of 14 eyes with visual potential. Of those, five eyes gained six or more lines, two eyes gained between four and five lines, six eyes gained between one and three lines, and one eye lost three lines of Snellen acuity. Pain and photophobia were abolished in 86% of cases and substantially reduced in 14%, with all eyes exhibiting decreased vascularisation and inflammation at final follow up. CONCLUSIONS: Amniotic membrane transplantation appears to be a safe and effective method of restoring a stable corneal epithelium for cases of partial limbal stem cell deficiency and can be considered as an alternative to limbal autograft or allograft.  (+info)

Mutations in the RPGR gene cause X-linked cone dystrophy. (6/64)

X-linked cone dystrophy is a type of hereditary retinal degeneration characterized by a progressive dysfunction of the day vision or photopic (cone) system with preservation of night vision or scotopic (rod) function. The disease presents with a triad of photophobia, loss of color vision and reduced central vision. This phenotype is distinct from retinitis pigmentosa (RP) in which there are prominent night and peripheral vision disturbances. X-linked cone dystrophy is a genetically heterogeneous disorder, with linkage to loci on Xp11.4--Xp21.1 (COD1, OMIM 304020) and Xq27 (COD2, OMIM 303800). COD1 maps to a region that harbors the RPGR gene, mutations in which account for >70% of patients with X-linked RP. The majority of these mutations reside in one purine-rich exon, ORF15, encoding 567 amino acids with a repetitive domain rich in glutamic acid residues. We mapped two families with X-linked cone dystrophy to the COD1 locus and identified two distinct mutations in ORF15 in the RPGR gene (ORF15+1343_1344delGG and ORF15+694_708del15) leading to a frame-shift and premature termination of translation in one case and a deletion of five amino acids in another. Consistent with expression of RPGR in rods and cones, our results show that mutations in RPGR, in addition to X-linked RP, can also cause cone-specific degeneration.  (+info)

A health intervention programme for children with albinism at a special school in South Africa. (7/64)

The genetic condition albinism has a high frequency among the Sotho people of northern South Africa. Affected children have pale hair, eyes and skin-a dramatic contrast to the normal dark pigmentation. Their visual performance is poor and many attend special schools for the visually impaired. Children with albinism experience problems that are, on the one hand, physiological, and, on the other, social-psychological and educational in nature. In this self-report study 38 children at a rural special school described their eye and skin problems, a direct result of their lack of pigmentation, as well as strategies they adopted to manage their condition. A further section of the study deals with the social adaptation difficulties experienced by these children. The questionnaire tested for local belief systems about albinism and how these impact on the socialization of children with albinism. The intervention strategy proposed in this study is based on the assumption that any attempt to address both the health and social problems should be of a holistic, interactionist nature, and be based on the values and belief systems of the local community. In addressing the physical problems, the proposed intervention programme focuses on sensible sun protection habits from a young age and the active participation of the children. To alleviate the social problems a team (interactionist) approach including children, teachers, parents, health officials and the wider community is recommended.  (+info)

Enteroviruses and sudden deafness. (8/64)

A young, healthy man presented with sudden severe sensorineural hearing loss and tinnitus. The results of the workup and neuroimaging were normal, as were the auditory brain stem responses. Methylprednisolone pulse therapy was associated with significant hearing improvement within 10 days. A history of a short self-limited febrile illness preceding admission (with headache, photophobia, myalgia and fatigue), a raised serum C-reactive protein level and transient leukopenia suggested an infectious cause. Lumbar puncture revealed a mononuclear pleocytosis of the cerebrospinal fluid, with negative cultures but positive polymerase chain reaction test results for enterovirus, which was later cultured from the patient's stool. The patient's wife and baby had had a similar febrile illness without hearing loss 10 days earlier, and an outbreak of enterovirus meningitis was identified in the area, which was associated with familial clustering and echovirus serotype 4 infection. The varied causes of sudden sensorineural hearing loss, which should include enterovirus, are reviewed here.  (+info)