1/22. choroideremia associated with subretinal neovascular membrane. PURPOSE: To report two Japanese patients with choroideremia, one male and one heterozygous female, who developed subretinal neovascular membrane and/or subretinal fibrosis in the intermediate stage of the disease, and, in addition, to describe marked clinical manifestation in a heterozygous carrier female. METHOD: Two patients were examined by slip-lamp biomicroscopy, ophthalmoscopy and other ophthalmoloscopic examinations. RESULTS: Two cases showed moderately advanced ophthalmoscopic and functional abnormalitities compatible with choroideremia, and in addition, subretinal lesion in the fovea and/or midperiphery. CONCLUSION: The intermediate stage of choroideremia may occasionally be complicated with choroidal neovascular membrane in the fovea, the midperiphery, or both, which resolves spontaneously and results in subretinal fibrous scarring. The occurrence of this complication in the fovea leads to episodic central visual loss, while midperipheral lesion may remain unrecognized. ( info) |
2/22. choroideremia, sensorineural deafness, and primary ovarian failure in a woman with a balanced X-4 translocation. We present clinical and cytogenetic studies of a female patient affected with choroideremia, mild sensorineural deafness, and primary amenorrhea showing a balanced translocation between chromosomes X and 4. The breakpoint was precisely defined applying FISH techniques: 46,X,t(X;4)(q21.2;p16.3).ish t(X;4)(D4S96 , D4F26 ; wcpX ). The X-chromosomal breakpoint was located within a region where both the choroideremia locus and a deafness locus (DFN3/POU3F4) have been mapped. The presence of X-linked disorders in this balanced carrier of X-autosomal translocations (XAT) can be explained either by the disruption of the structural coding or regulatory sequences of the gene(s) or by the submicroscopic deletion of this region leading to a contiguous gene deletion syndrome. The primary ovarian failure (POF) found in the present case has been already observed in XAT when the breakpoint is within a previously defined critical region (Xq13-26). A position effect is postulated as a possible explanation. ( info) |
3/22. Evaluation of retinal photoreceptors and pigment epithelium in a female carrier of choroideremia. PURPOSE: To clarify the pathogenesis of choroideremia. STUDY DESIGN: Human tissue study. tissues: Eyes of an 88-year-old symptomatic female carrier of choroideremia (CHM) and six normal, age-matched donors. methods: The eyes were processed for histopathologic examination, including immunocytochemistry with an antibody against the CHM gene product, REP-1, and retinal cell-specific markers. RESULTS: The CHM carrier retina showed patchy degeneration, but the photoreceptor and retinal pigment epithelium (RPE) loss appeared to be independent. The choriocapillaris was normal except where retinal areas were severely degenerate. The CHM gene product, REP-1, was localized to the cytoplasm of rods but not cones. CONCLUSIONS: It has generally been considered that photoreceptor degeneration in CHM is secondary to loss of the choriocapillaris or RPE. This study suggests that the rod photoreceptors are a primary site of disease in CHM. ( info) |
4/22. A case of choroideremia with recurrent anterior uveitis. choroideremia is a rare hereditary disease with characteristic fundus that causes night blindness and peripheral visual field loss. The authors encounter choroideremia accompanied by recurrent uveitis. This paper is designed to give a description of the condition, along with an investigation of the literature. Ophthalmological tests and treatments were performed. Characteristic fundus, night blindness, peripheral visual field loss, electroretinography and other manifestations led us to a diagnosis of choroideremia. The anterior uveitis was managed with medication. ( info) |
5/22. Clinical diagnoses that overlap with choroideremia. PURPOSE: To understand which clinical presentations suggest a diagnosis of choroideremia (CHM). methods: Retrospective chart review. Included were patients for whom a clinical diagnosis of CHM was suggested, but either protein analysis or direct sequencing of the CHM gene could not confirm the diagnosis. Clinical presentation, family history and fundus photographs were reviewed. RESULTS: We analyzed protein and dna samples from members of more than 100 families in which at least 1 member had a clinical diagnosis of CHM. For 26 of these families, the clinical diagnosis of CHM could not be confirmed by laboratory analysis. Relevant clinical information was requested from the referring ophthalmologists so that alternative diagnoses could be considered. Sufficient information was provided for 13 of the 26 families. Four patients were reclassified as having retinitis pigmentosa (RP) from the clinical phenotype; only two clearly had X-linked inheritance. One patient had a syndrome including macular dystrophy, hearing loss, developmental delay and cerebral palsy. One patient was reclassified as having congenital stationary night blindness on the basis of an electronegative electroretinogram and a normal fundus. One patient had hearing loss suggesting Usher syndrome. One patient had signs consistent with cone-rod dystrophy (CRD). Five patients could not be reclassified on the basis of the clinical presentation. CONCLUSION: RP, Usher syndrome and CRD are clinical phenotypes that may overlap with CHM. Clinical features that suggest CHM include severe chorioretinal atrophy with preservation of the macula, X-linked inheritance and retinal changes in a related female. ( info) |
6/22. Prenatal exclusion of choroideremia. We performed prenatal testing to predict the inheritance of choroideremia (CHM) using a linked polymorphic dna marker, DXS95. dna analysis of chorionic villi at the 12th week of pregnancy indicated that the allele at risk had not been passed from the heterozygous mother to the fetus. This prenatal exclusion of choroideremia was confirmed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. ( info) |
7/22. Phenotypic variability in three carriers from a family with choroideremia and a frameshift mutation 1388delCCinsG in the REP-1 gene. PURPOSE: To perform genotype-phenotype correlations in a family with choroideremia. methods: A three-generation family with two affected males and five carriers was the subject of the study. Molecular genetic analysis using single-strand conformation polymorphism analysis (SSCP) was conducted in all subjects, while electroretinography (ERG), multifocal ERG (mfERG), scanning laser ophthalmoscope microperimetry (SLO perimetry), fluorescein angiography, and Arden contrast color testing were performed in one male and three carriers. RESULTS: The findings in the affected male were typical for advanced choroideremia. The three carriers demonstrated a variable clinical phenotype including reduction of visual acuity and ERG and angiographic changes in one. Molecular genetic analysis revealed a functional null mutation (1388delCCinsG) in the REP-1 gene. CONCLUSIONS: A severe retinal pathology was found in the affected male, indicating that the 1388delCCinsG is a severe mutation. Varying phenotypes were present in the three carriers examined. The phenotype in carriers has been explained by random X-inactivation with varying expression of the inactivated and activated gene copy inside the same cell of both the retinal pigment epithelium and the rods. This thesis is in agreement with the clinical data obtained here. ( info) |
8/22. Detection of localized retinal dysfunction in a choroideremia carrier. PURPOSE: To investigate severe unilateral vision loss in a choroideremia carrier. DESIGN: Case report. methods: Ocular examination, genetic testing, Humphrey visual fields, full-field and multifocal (mf) electroretinogram (ERG) tests were used to study a family with choroideremia. RESULTS: In a carrier with unilateral central vision loss, mfERG showed severely reduced amplitudes which correlated with a band of retinal pigment epithelial and choroidal atrophy in the macula, a dense central scotoma on Humphrey visual fields testing, and decreased ERG amplitudes. CONCLUSIONS: Multifocal ERG may be a sensitive tool to measure functional abnormalities in choroideremia carriers. Mosaic inactivation of the normal gene may cause expression of the mutation with severe vision loss in choroideremia carriers. ( info) |
9/22. Clinical findings in a carrier of a new mutation in the choroideremia gene. OBJECTIVE: To describe the clinical and molecular findings of a female carrier of a new mutation in the choroideremia (CHM) gene. DESIGN: Single interventional case report. methods: A 27-year-old woman was seen with mild difficulties with dark adaptation and a history of a retinal degeneration in her father and choroideremia in 3 male paternal first cousins. visual acuity measurements, peripheral and color vision tests, electroretinography (ERG), Goldmann visual fields, fluorescein angiogram, computed tomography scan, and dna analysis were performed. MAIN OUTCOME MEASURES: (1) visual fields, (2) fluorescein angiography, and (3) dna analysis. RESULTS: visual acuity decreased from 20/30 to 10/200 in the right eye abruptly over 2 months, then remained stable over 2 years of follow-up and remained 20/25 in the left eye. Goldmann visual fields showed development of a central scotoma in the right eye concurrent with the rapid decline. A small amount of subretinal hemorrhage was visible on dilated fundus examination at that time, but definite leakage was not evident on fluorescein angiography; afterwards, a choroidal neovascular membrane (CNV) was suspected. The ERG was normal. dna analysis revealed that the patient was heterozygous for a previously undescribed substitution mutation at the 3'-splice site of intron 6 of the CHM gene (850-1 G to C), confirmed by mRNA analysis with reverse transcriptase polymerase chain reaction. CONCLUSIONS: Severe visual acuity loss rarely occurs in female carriers of choroideremia mutations. The diagnosis should be considered in patients with a suitable family history and fundus findings. physicians should consider the possibility of CNV development in such patients, which may be a response to abnormal retinal pigment epithelium. Recognition of this new mutation may help identify patients who could benefit from current and future treatments to protect against vision loss. ( info) |
10/22. Clinical features of Japanese families with a 402delT or a 555-556delAG mutation in choroideremia gene. PURPOSE: To characterize the clinical features of two Japanese families with choroideremia associated with a 402delT and a 555-556delAG mutation in the choroideremia gene (CHM). methods: Four affected members and one obligate carrier from two Japanese families with choroideremia were studied. To detect mutations of the CHM gene, the products of polymerase chain reaction were directly sequenced in both directions. The ophthalmologic examination included best-corrected visual acuity, slit-lamp examination, fundus examination, kinetic perimetry, electroretinography, and fluorescein angiography. RESULTS: A 402delT and a 555-556delAG mutation were found in two Japanese families with choroideremia. All affected members had night-blindness, progressive constriction of the visual field, chorioretinal atrophy, and mottled appearance of the retinal pigment epithelium. The obligate carrier had mild patchy areas of retinal pigment epithelial atrophy with no visual symptoms. CONCLUSION: The authors found a 402delT and a 555-556delAG mutation in the CHM gene, one of which (402delT) is a novel mutation. They conclude that these mutations cause choroideremia in Japanese families. ( info) |