Characterizing the Phenotype and Genotype of a Family With Occult Macular Dystrophy

Archives of ophthalmology (Impact Factor: 4.4). 12/2012; 130(12):1554-9. DOI: 10.1001/archophthalmol.2012.2683
Source: PubMed


To characterize the phenotype of a white patient with occult macular dystrophy (OMD) and her clinically unaffected family members and to determine whether similar mutations were present in the RP1L1 gene in this family. Occult macular dystrophy is a rare macular dystrophy with central cone dysfunction hidden behind a normal fundus appearance that has been attributed to a mutation in the retinitis pigmentosa 1-like 1 (RP1L1) gene in 4 Japanese families.

In this observational cross-sectional study of 1 white family with OMD, patients meeting the clinical criteria for OMD and their family members were evaluated by use of multifocal electroretinography, the Farnsworth D-15 color vision test, automated perimetry, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, and fundus photography. Fluorescein angiography was performed only on the proband. Members of this family were screened for genetic mutations in the RP1L1 gene.

In the family studied, the clinically affected proband was noted to have loss of the foveal outer segments and absence of bowing of the inner segment/outer segment junction on SD-OCT scans. In addition, 1 clinically unaffected family member also demonstrated loss of the foveal photoreceptor outer segments and, therefore, decreased bowing of the inner segment/outer segment junction on SD-OCT scans. The fundus autofluorescence images of the eyes of the proband and her family members were normal. Although mutations in the RP1L1 gene have been identified in sporadic and autosomal dominant OMD pedigrees, no mutations in the RP1L1 gene were found in any of the participants.

Loss of the outer segments of foveal photoreceptors can be detected and quantified by use of SD-OCT in patients with OMD. Similar findings are present in some clinically unaffected family members and may represent subclinical manifestations of the disease. Although mutations in the RP1L1 gene have been described in several Japanese families with OMD, there were no such mutations in this white family of European descent, which suggests that inherited OMD is a genetically heterogeneous disorder.

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    • "Our case did not show any mutations in the RP1L1 gene by genetic testing. Because in a previous study, no mutations were detected in four patients with OMD from a single Caucasian family,13 OMD is considered to be a genetically heterogeneous disorder. "
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    ABSTRACT: To investigate changes in cone photoreceptors with adaptive optics (AO) fundus imaging and spectral domain optical coherence tomography (SD-OCT) in a case of occult macular dystrophy (OMD). Both eyes of a 42-year-old woman diagnosed with OMD were examined. We used an AO fundus camera to obtain images of cone photoreceptors in the macula of the OMD subject and five healthy control subjects. Correlations between the AO images and the SD-OCT images were examined. Cone photoreceptors in eight areas in the macula of OMD and healthy control subjects were analyzed and compared. SD-OCT showed a loss of the cone outer-segment tips line outside of the fovea in both eyes of the subject with OMD. The left eye with decreased visual acuity showed a discontinuous photoreceptor inner-segment and outer-segment line and cone outer-segment tips line at the fovea in SD-OCT and loss of cone mosaics as a dark spot in the AO image. In panoramic AO images and cone-density maps, less cone density was observed in a ring-like region outside the fovea than in the peripheral retina. In most of the areas examined, the cone densities were lower in the OMD eyes than in the healthy control eyes. Cone densities in the macula of the OMD patient were greatly decreased. AO images were found to be useful to evaluate morphologic changes in cone photoreceptors in patients with OMD.
    Full-text · Article · May 2013 · Clinical ophthalmology (Auckland, N.Z.)
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    ABSTRACT: Purpose: We investigated the genetic characteristics of retinitis pigmentosa 1-like 1 (RP1L1) gene in patients with occult macular dystrophy (OMD) and identified genotype-phenotype correlations. Methods: We sequenced the entire exons and flanking regions of the RP1L1 gene in 19 Korean OMD patients. Detailed retinal morphologic abnormalities were evaluated using spectral domain optical coherence tomography and infrared reflectance imaging. Clinical features, retinal morphologic abnormalities, and disease progression were compared among the subtypes separated on the basis of genotypes. Results: Ten of 19 (52.6%) patients had RP1L1 mutations: 7 (36.8%) had the previously reported mutation, p.Arg45Trp, and the other 3 (15.8%) had novel variants (p.Gln2311Pro, p.Ser676Cys, and p.Asp1425His). p.Gln2311Pro, p.Asp1425His, and p.Ser676Cys were predicted as pathogenic in 3, 2, and none of 5 computational assessment tools, respectively. Photoreceptor disruption across the fovea was symmetric in all eyes with RP1L1 mutations, but asymmetric in 3 eyes without the mutations. Symmetric round hyporeflectance centered on the fovea in infrared reflectance images was seen in all patients with the p.Arg45Trp mutation, but in only 2 of 12 patients without the mutation. The patients with p.Arg45Trp showed greater extent of photoreceptor disruption than those without the mutation. Progression of photoreceptor disruption was remarkable in patients with RP1L1 mutations, but insignificant in those without. Conclusions: OMD is clinically and genetically heterogeneous, with different morphologic features and progression in outer retinal pathology according to RP1L1 gene mutations, indicating the genotype-phenotype correlation in patients with OMD.
    Full-text · Article · Jun 2013 · Investigative ophthalmology & visual science
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    ABSTRACT: To determine whether a significant correlation exists between the presence of a bulge in the photoreceptor inner segment/outer segment (IS/OS) line and the best-corrected visual acuity (BCVA) in eyes with resolved macular edema associated with branch retinal vein occlusion (BRVO). Retrospective, observational case series. We retrospectively reviewed the medical records of patients who had a complete resolution of macular edema and had an intact IS/OS line in the central fovea in the spectral-domain optical coherence tomographic (SDOCT) images. Thirty-one eyes with macular edema associated with BRVO (BRVO group) and 31 unaffected fellow eyes (control group) of 31 patients were evaluated. In normal eyes, the intact IS/OS line determined by SDOCT has a bulge at the central fovea, called the foveal bulge. The eyes in the BRVO group were classified by the presence or absence of foveal bulge, and the characteristics of the 2 groups were compared. A foveal bulge was present in 7 of 31 eyes in the BRVO group. The incidence of a foveal bulge was significantly lower in the BRVO group (22.6%) than in the control group (100%; P < .0001). All 7 eyes with foveal bulge had a decimal BCVA of ≥1.0 at the final visit. The incidence of a foveal bulge was significantly higher in eyes with BCVA of ≥1.0 (77.8%) than in the eyes with BCVA of <1.0 (0%; P < .0001). The foveal bulge is a good marker of the functional properties of the fovea in eyes with resolved macular edema associated with BRVO.
    No preview · Article · Feb 2014 · American Journal of Ophthalmology
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