Association of Major Histocompatibility Complex Class I Chain-Related Gene <Emphasis Type="Italic">A</Emphasis> and <Emphasis Type="Italic">HLA-B</Emphasis> Alleles with Behçet's Disease in Turkey

Purpose

Behçet's disease (BD) is known to be associated with HLA-B*51 in many different ethnic groups. Recently, the major histocompatibility complex class I chain-related gene A (MICA), located near the HLA-B gene, has been proposed as a candidate gene for BD susceptibility in several ethnic groups. To compare the relative contribution of MICA polymorphisms and HLA-B*51 to BD in different ethnic groups, we studied MICA polymorphisms in Turkish BD patients.

Methods

Thirty-three Turkish BD patients and 65 healthy controls were enrolled for analysis of polymorphisms in the extracellular domains of MICA.

Results

The phenotype frequencies of MICA*009 were significantly higher in BD patients (75.8%) than in controls (29.2%) (P = 0.000015). HLA-B*51 was also significantly more frequent in BD patients (81.8%) than in controls (29.2%) (P = 0.0000007). A strong association existed between MICA*009 and HLA-B*51. To assess the confounding effect of MICA*009 on HLA-B*51, we performed a stratification analysis that showed that BD was distinctly associated only with HLA-B*51.

Conclusion

Our results indicate that the major susceptibility gene for BD is HLA-B*51 and that the association between MICA*009 and BD arises from a strong linkage disequilibrium with HLA-B*51. However, we suggest that MICA*009 likely elicits an immune effect secondary to BD.?Jpn J Ophthalmol 2007;51:431–436 © Japanese Ophthalmological Society 2007

     

Excellent visual outcome following <Emphasis Type="Italic">Aspergillus flavus</Emphasis> endogenous endophthalmitis—farmer’s lung disease

Introduction The purpose is to report an eye with endogenous Aspergillus flavus endophthalmitis that achieved a good visual outcome following early and aggressive management. Methods A 76-year-old male recently hospitalized for allergic Aspergillus pneumonitis after cleaning out a grain bin presented with reduced vision and anterior chamber and vitreous inflammation. The patient was treated with intravenous amphotericin and a pars plana vitrectomy with intravitreal amphotericin, and the vitreous biopsy sent for histopathological and microbial analysis. Results A. flavus was isolated from the vitreous biopsy. Two weeks after vitrectomy, intravitreal amphotericin was again injected into the affected eye. The patient regained vision to 20/80 several months later, despite a moderate cataract. Conclusion Early treatment of A. flavus endophthalmitis with pars plana vitrectomy, intravitreal and systemic amphotericin can lead to good visual outcomes.     

von Hippel–Lindau disease type 2A in a family with a duplicated 21-base-pair in-frame insertion mutation in the<Emphasis Type="Italic"> VHL</Emphasis> gene

BACKGROUND: von Hippel-Lindau disease (VHL), also called angiomatosis retinae, is inherited as an autosomal dominant trait. It is frequently associated with other tumors in the central nervous system, kidneys, or adrenal glands. In order to investigate the relationship between genotype and corresponding phenotypes, we performed molecular genetic analysis in a Japanese patient with VHL type 2A. METHODS: After informed consent had been obtained, the three exons of the VHL gene were PCR-amplified and sequenced either directly or after subcloning. Clinical features were also examined. RESULTS: A novel in-frame duplication of the 21 base pairs at nucleotide 806 (the position of codon 198) of the VHL gene was found in our patient. The clinical phenotype of the patient included retinal hemangiomas associated with vitreous hemorrhage and traction retinal detachment, pheochromocytoma, and hemangioma-like lesions in the cerebellum which corresponded to those of VHL type 2A. Abnormal diffuse vascular leakage was observed in the apparently intact retina by fluorescein angiography. CONCLUSION: An insertion mutation of the VHL gene is a rare association with VHL type 2. This insertion mutation may interfere the binding between the VHL gene and elongins. Abnormal retinal vascular leakage suggests the possible effects of overexpressed vascular permeability factors such as vascular endothelial growth factor from hemangiomas associated with defective VHL gene.     

Gyrate atrophy: clinical and genetic findings in a female without arginine-restricted diet during her first 39 years of life and report of a new <Emphasis Type="Italic">OAT</Emphasis> gene mutation

We report the clinical and genetic data obtained at a 17-year follow-up examination of a patient with gyrate atrophy, without an arginine-restricted diet. Patient examinations included visual acuity (VA), perimetry, biomicroscopy, funduscopy, fundus photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (OCT), and standard full-field electroretinography (ERG). Blood samples were taken for measurement of serum ornithine level and molecular genetic analysis of the OAT gene. The female was 22 years of age when gyrate atrophy was diagnosed based on peripheral chorioretinal atrophy and an increased ornithine level. Reexamination after 17 years revealed a reduced VA (0.25 OU), dense cataract, extensive peripheral chorioretinal atrophy, a further increased ornithine level, but only slow progression of visual field constriction, and still detectable ERG amplitudes. FAF was absent in the atrophic periphery and almost homogeneous at the posterior pole except parafoveally. OCT showed interruption of the foveal inner/outer segment junction and parafoveal microcystoid spaces. After cataract surgery, VA increased to the same values as those found at the age of 22 years (0.5 OD, 0.6 OS). Molecular analysis revealed a new deletion c.532_536delTGGGG (p.Trp178X) and a known mutation c.897C>G (p.Tyr299X) in the OAT gene. Although the patient had refused to diet during her first 39 years of life, the gyrate atrophy showed a very slow progression. FAF allows evaluating the integrity of the retinal pigment epithelium and may help to delimit gyrate atrophy from choroideremia. Interruption of foveal inner/outer segment junction and cystoid macula edema appears in gyrate atrophy.     

<Emphasis Type=Italic>Aspergillus keratitis</Emphasis> in vernal shield ulcer—a case report and review

An unusual case of vernal shield ulcer with superadded fungal keratitis caused by Aspergillus fumigates is reported. A 26-year-old man, a known case of vernal keratoconjunctivitis (VKC) presented with the complaint of diminution of vision in the right eye. Patient was on topical steroids and anti-allergic treatment for the past two months. In the right eye, a shield ulcer with an elevated plaque was seen. Scrapings from the right cornea revealed fungal filaments on a wet KOH mount and culture revealed growth of Aspergillus fumigatus. The patient was diagnosed as VKC with shield ulcer with secondary fungal keratitis. The patient was treated with topical cyclosporine, topical moxifloxacin, topical natamycin, and topical amphotericin eye drops. The patient responded well and finally recovered to a best spectacle-corrected visual acuity of 20/20 at the end of nine months. The chronic ocular surface changes and induced inflammation in VKC, and the instillation of topical steroids for therapy, may create an environmental milieu favorable for fungal keratitis. Microbiological evaluation should be considered, even in cases of suspected sterile keratitis, to prevent possible worsening of an associated infective corneal condition. This warrants patient education, periodic reviews and a very cautious approach to indiscriminate use of topical corticosteroids in cases of VKC with shield ulcer. In the event of any secondary fungal infection, use of steroid sparing topical agent, for example cyclosporine may be considered.