1/25. Juvenile retinoschisis: a model for molecular diagnostic testing of X-linked ophthalmic disease.BACKGROUND AND PURPOSE: X-linked juvenile retinoschisis (RS) provides a starting point to define clinical paradigms and understand the limitations of diagnostic molecular testing. The RS phenotype is specific, but the broad severity range is clinically confusing. Molecular diagnostic testing obviates unnecessary examinations for boys at-risk and identifies carrier females who otherwise show no clinical signs. methods: The XLRS1 gene has 6 exons of 26-196 base-pair size. Each exon is amplified by a single polymerase chain reaction and then sequenced, starting with exons 4 through 6, which contain mutation "hot spots." RESULTS: The 6 XLRS1 exons are sequenced serially. If alterations are found, they are compared with mutations in our > 120 XLRS families and with the > 300 mutations reported worldwide. Point mutations, small deletions, or rearrangements are identified in nearly 90% of males with a clinical diagnosis of RS. XLRS1 has very few sequence polymorphisms. Carrier-state testing produces 1 of 3 results: (1) positive, in which the woman has the same mutation as an affected male relative or known in other RS families; (2) negative, in which she lacks the mutation of her affected male relative; and (3) uninformative, in which no known mutation is identified or no information exists about the familial mutation. CONCLUSIONS: Molecular RS screening is an effective diagnostic tool that complements the clinician's skills for early detection of at-risk males. Useful outcomes of carrier testing depend on several factors: (1) a male relative with a clear clinical diagnosis; (2) a well-defined inheritance pattern; (3) high disease penetrance; (4) size and organization of the gene; and (5) the types of disease-associated mutations. Ethical questions include molecular diagnostic testing of young at-risk females before the age of consent, the impact of this information on the emotional health of the patient and family, and issues of employability and insurance coverage.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
2/25. Hereditary retinal dystrophies and choroidal neovascularization.BACKGROUND: choroidal neovascularization infrequently occurs in patients affected by hereditary retinal dystrophies. methods: We studied eight patients suffering from different hereditary retinal dystrophies (Best's disease, reticular dystrophy, butterfly-shaped dystrophy, gyrate atrophy, and retinitis pigmentosa) who developed choroidal neovascularization. All patients underwent complete ophthalmic evaluation, electrophysiology, colour vision testing, and fluorescein angiography. In some patients, ICG video-angiography was also performed. Laser treatment was carried out in only one patient. RESULTS: The mean duration of follow-up was 41.7 months (range 6-148 months). At CNV diagnosis, the mean VA was 0.23 (range 0.02-0.6). At the last follow-up, mean VA was 0.34 (range HM to 0.9). At the last follow-up, fluorescein angiography showed a focal, atrophic scar in seven eyes, a fibrotic membrane in two eyes and a still active membrane in two cases. CONCLUSION: We emphasize the relatively favourable visual prognosis in patients suffering from inherited retinal dystrophies complicated with choroidal neovascularization. Therapeutic approaches other than laser treatment could be attempted in these patients.- - - - - - - - - - ranking = 0.5keywords = size (Clic here for more details about this article) |
3/25. Pattern dystrophy of the retinal pigment epithelium in Crohn's disease. A case report.The authors describe a case of bilateral pattern dystrophy of the retinal pigment epithelium in a man with Crohn's disease. The patient was examined every 6 months over a follow-up of 30 months. The right eye presented a macroreticular dystrophy while in the left eye a butterfly pattern dystrophy was diagnosed. During the follow-up period the retinal lesion changed; in the right eye the lesion increased in size, while in the left eye the morphology of the lesion passed from the butterfly to Sjogren's type. This report adds a new ocular manifestation of Crohn's disease, emphasizing the importance of the ophthalmological follow-up in the recognition of posterior segment complications associated with this inflammatory bowel disease.- - - - - - - - - - ranking = 0.5keywords = size (Clic here for more details about this article) |
4/25. Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa.mutation of a receptor tyrosine kinase gene, Mertk, in the Royal College of Surgeons (RCS) rat results in defective phagocytosis of photoreceptor outer segments by the retinal pigment epithelium (RPE) and retinal degeneration. We screened the human orthologue, MERTK, located at 2q14.1 (ref. 10), in 328 dna samples from individuals with various retinal dystrophies and found three mutations in three individuals with retinitis pigmentosa (RP). Our findings are the first conclusive evidence implicating the RPE phagocytosis pathway in human retinal disease.- - - - - - - - - - ranking = 0.88726756886355keywords = sample (Clic here for more details about this article) |
5/25. Atypical presentation of pattern dystrophy in two families with peripherin/RDS mutations.PURPOSE: To describe the atypical clinical presentations of pattern dystrophy (PD) in two unrelated families with novel peripherin/RDS mutations. DESIGN: Observational case reports and family genetic study with review of peripherin/RDS mutations. PARTICIPANTS: Affected and unaffected members of two families with PD. methods: The probands of two families, as well as other family members, underwent an ophthalmologic assessment including slit-lamp biomicroscopy, applanation tonometry, and a dilated fundus examination. Goldmann visual fields and fluorescein angiography were performed, wherever appropriate. blood samples were obtained from affected and selected unaffected members of the families for dna analysis. RESULTS: The proband of family 1 had an acute onset of decreased vision and a yellowish lesion in both maculae that appeared inflammatory. However, resolution of the acute lesion ultimately resulted in fundus changes more typical for PD. Moreover, the proband's sister showed more classic-appearing PD lesions. Screening of the peripherin/RDS gene for sequence variations showed a 2-bp deletion, resulting in a translational frameshift at codon 290 in affected members of the family. The proband's father, who showed this sequence variation, did not have a macular lesion. The proband of family 2 was asymptomatic and showed a fundus phenotype similar to fundus flavimaculatus. The patient had normal visual acuity and did not demonstrate a "dark choroid" on fluorescein angiography. Molecular screening showed a Gln331stop variation in the peripherin/RDS gene. CONCLUSIONS: We describe two novel mutations in the peripherin/RDS gene in two unrelated families with PD. Clinicians should recognize the atypical features that may occur in patients with PD. A suspected diagnosis of PD may be confirmed by the identification of a mutation in the peripherin/RDS gene. In isolated family members with PD, a mutation in this gene may occur even in the absence of a clinically discernible macular lesion.- - - - - - - - - - ranking = 0.88726756886355keywords = sample (Clic here for more details about this article) |
6/25. Persistent intraschisis hemorrhage simulating choroidal melanoma.BACKGROUND: Intraschisis hemorrhage of dark green color without accompanying vitreous hemorrhage is a rare complication of degenerative retinoschisis-detachment. CASE: A 37-year-old male patient with unilateral intraschisis hemorrhage closely mimicking a choroidal melanoma is described. OBSERVATIONS: ultrasonography and intravenous fluorescein angiography suggested intraschisis hemorrhage. T(1)-weighted magnetic resonance imaging demonstrated a hyperintense lesion compared to the vitreous that did not enhance with contrast agent. Managed by observation, the color of the lesion started to change at the 6th month of follow-up. The hemorrhagic lesion regressed to half size in 40 months following the diagnosis, and disappeared in 62 months. CONCLUSION: Very rarely may an intraschisis hemorrhage secondary to degenerative retinoschisis-detachment simulate a choroidal melanoma. In our patient, careful interpretation of the conventional methods was adequate for the differential diagnosis. The unusual feature of this patient was that the hemorrhage resolved in 5 years, much slower than expected.- - - - - - - - - - ranking = 0.5keywords = size (Clic here for more details about this article) |
7/25. Reticular tapeto-retinal dystrophy. As a possible late stage of Sjogren's reticular dystrophy.Findings from two patients with a reticular tapetoretinal dystrophy strongly suggested advanced stages of Sjogren's reticular dystrophy. These observations emphasize that, although initially a benign disease, advanced stages of Sjorgren's dystrophy may eventually manifest diffuse photoreceptor and retinal pigment epithelial disease.- - - - - - - - - - ranking = 0.5keywords = size (Clic here for more details about this article) |
8/25. adult-onset foveomacular vitelliform dystrophy with OCT 3.PURPOSE: To report the morphologic data of adult-onset foveomacular vitelliform dystrophy (AFVD) provided by third-generation optical coherence tomography (OCT 3). DESIGN: Observational case report. methods: An 85-year-old woman presenting with AFVD underwent fundus biomicroscopy, fluorescein angiography, and OCT examination. RESULTS: Fundus examination disclosed a round, elevated yellowish lesion, centered by a pigmented spot, in the macula of the left eye. Examination with OCT disclosed an area of hyperreflectivity located between the retinal pigment epithelium layer and the photoreceptor layer, compatible in size with the yellowish elevated lesion. The hyperreflective line corresponding to the photoreceptor layer was elevated by the material and separated from the retinal pigment epithelium layer. CONCLUSIONS: In AFVD, examination with OCT 3 demonstrates elevation of the photoreceptor layer by the material and supports the previous hypothesis that the material is located between the photoreceptor and the retinal pigment epithelium layer.- - - - - - - - - - ranking = 0.5keywords = size (Clic here for more details about this article) |
9/25. CYP4V2 mutations in two Japanese patients with Bietti's crystalline dystrophy.Bietti's crystalline dystrophy (BCD) is an autosomal-recessive retinal dystrophy characterized by numerous glistening intraretinal dots scattered over the fundus, particularly in the posterior pole. The purpose of this study was to report mutations in the CYP4V2 gene (encoding a ubiquitously-expressed 525-amino acid sequence belonging to the CYP450 family) and to investigate the impact of the mutation on pre-mRNA splicing. dna and rna analyses were conducted using blood samples from two unrelated Japanese patients with BCD (a 46-year-old female and a 52-year-old male). In the female patient, a homozygous deletion/insertion mutation (g.IVS6-8_-1delc.802_810del/insGC) including the 3 -acceptor splice site was identified. reverse transcription-PCR analysis revealed that the complete length of exon 7 (186 bp), is skipped, resulting in the in-frame deletion mutation (p.V268_E329del). Conversely, the male patient was a compound heterozygote for the deletion/insertion and novel nonsense (p.W340X) mutations. Clinically, the female patient had decreased visual acuity, constriction of visual fields, severely reduced amplitudes in both rod and cone electroretinograms (ERGs). Despite being 6 years older, the male patient presented with milder clinical manifestations having good visual acuity and substantial amplitudes in both rod and cone ERGs. Because the CYP4V2 truncated protein with the p.W340X mutation lacks 186 amino acids at the C-terminus, if expressed, it retains 62 amino acids encoded in exon 7, which are important for enzymatic activity. In the male patient, expression of both mutant alleles may compensate for the malfunction of each mutated protein and could explain why a milder form of BCD results from compound heterozygosity.- - - - - - - - - - ranking = 0.88726756886355keywords = sample (Clic here for more details about this article) |
10/25. Clinical and molecular findings in three Japanese patients with crystalline retinopathy.PURPOSE: To identify CYP4V2 mutations in three unrelated Japanese patients with Bietti crystalline corneoretinal dystrophy (BCD). methods: The three cases were diagnosed by ophthalmological examinations. All exons and flanking introns were amplified by polymerase chain reaction (PCR). PCR products were analyzed by direct sequencing. rna was extracted from blood samples and analyzed by reverse transcriptase (RT)-PCR sequencing. RESULTS: Direct PCR sequencing demonstrated a homozygous mutation involving a 17-bp deletion together with a 2-bp insertion (c.802-8del17bp/insGC) in case 1 and case 3, and RT-PCR demonstrated that the complete length of exon 7 was missing; case 2 showed only a heterozygous change in exon 11 with no second mutation. CONCLUSION: A homozygous mutation was identified in two of the unrelated patients, and only a heterozygous change was detected in the third. These data indicate that c.802-8del17bp/insGC may be a frequent mutation in this gene.- - - - - - - - - - ranking = 0.88726756886355keywords = sample (Clic here for more details about this article) |
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