Biomedical subjects

G A Fishman

Publications and source records attributed to G A Fishman.

At least 19 recordsLinked to original sources

PubMed2006

Attainment of educational levels in patients with Leber's congenital amaurosis.

PURPOSE: To assess the educational level attained by patients legally blind with Leber's congenital amaurosis (LCA). DESIGN: Cross-sectional assessment. INTERVENTION: None. MAIN OUTCOME MEASURE: Highest educational level attained by 55 patients with LCA. RESULTS: A total of 55 patients with LCA were included in the study. Of the 55, 54 finished high school. In addition, 36 patients (65%) completed a college education and received a bachelor's degree, and 5 additional patients (9%) were recently accepted to college, whereas 3 others (5%) were currently attending college classes. Further, 18 patients were either pursuing (n = 3) or had attained (n = 15) an educational level beyond a bachelor's degree. CONCLUSIONS: Compromised visual function does not preclude the successful attainment of an academic education in patients with LCA who are substantially visually impaired from birth. These data have clinically relevant implications for the parents of children with LCA and for the patients themselves in providing a tone of optimism for their potential of attaining competitive academic achievements.

Adult↗

PubMed2003

Interocular amplitude differences of the full field electroretinogram in normal subjects.

AIMS: To determine the interocular amplitude response difference of the electroretinogram (ERG) in normal subjects. METHODS: 79 subjects, without retinal changes of clinical significance, underwent ERG testing. They included 63 men and 16 women, with a mean age of 44 (SD 12) years and range of 18-65 years. Isolated rod, scotopic maximal, dark adapted 30 Hz flicker, photopic single flash, and light adapted 30 Hz flicker responses were recorded in both eyes following the International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocol. The interocular percentage differences of the ERG b-wave amplitudes were calculated and presented as percentiles (25th, 50th, 75th, 95th), means (SD), and medians. RESULTS: The median interocular percentage differences in the b-wave amplitudes for the above ERG stimulus responses were 10%, 8%, 10%, 11%, and 10%, respectively. The mean interocular percentage differences were 11%, 11%, 12%, 13%, and 14%. The 95th percentiles for the interocular percentage differences were 28%, 27%, 36%, 33%, and 35%, respectively. CONCLUSIONS: The interocular percentage differences in the ERG b-wave amplitudes for five different stimulus responses were similar in our cohort of individuals without clinically significant retinal changes and ranged from a median of 8-11% and a 95th percentile of 27-36%. Our findings should be useful for determining sample sizes in future therapeutic trials on retinal diseases with monocular therapeutic strategies and may also have application for the more accurate detection of asymmetric retinal disease.

Adaptation, Ocular↗

PubMed2002

Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia.

BACKGROUND/AIMS: Few studies have reported on the change in visual acuity (VA) in patients with choroideraemia. In order to determine the degree and rate of VA impairment associated with this disease, the central VA was analysed in a large group of patients with choroideraemia. METHODS: The authors completed a retrospective, cross sectional review of 115 patients with choroideraemia from three tertiary care centres. A longitudinal analysis was performed on 45 of these patients who met the inclusion criteria of at least three visits over a minimum period of 4.5 years. Multiple linear regression analysis was used to explore the 5 year rate of VA change while controlling for initial VA and initial age. Multiple logistic regression was also used to investigate VA impairment. RESULTS: In the cross sectional group (n = 115), 84% (87/103) of patients under the age of 60 had a VA of 20/40 or better while 33% (4/12) of patients 60 years of age or older had a VA of 20/200 or worse at their most recent visit. The majority of the patients (93%) in the longitudinal subgroup of 45 patients had a VA of 20/30 or better at their initial visit. The mean 5 year rate of VA change was 0.09 logMAR equivalent (approximately one line on the Lighthouse chart). CONCLUSION: In this cohort of patients with choroideraemia, there was typically a slow rate of VA loss and the prognosis for central VA retention was, as a group, favourable until the seventh decade.

Adolescent↗

PubMed2001

Mutations in the CRB1 gene cause Leber congenital amaurosis.

OBJECTIVES: To test the hypothesis that mutations in the CRB1 gene cause Leber congenital amaurosis (LCA) and, if so, to describe the ocular phenotype of patients with LCA who harbor CRB1 sequence variations. PATIENTS: One hundred ninety probands with a clinical diagnosis of LCA were selected from a cohort of 233 probands ascertained in 5 different countries. The remaining 43 probands (18%) were excluded because they harbored sequence variations in previously identified LCA genes. METHODS: One hundred ninety unrelated individuals with LCA were screened for coding sequence mutations in the CRB1 gene with single-strand conformation polymorphism analysis followed by automated DNA sequencing. RESULTS: Twenty-one of the 190 probands (9% of the total cohort of 233) and 2 (1.4%) of 140 controls harbored amino acid-altering sequence variations in the CRB1 gene (P =.003). CONCLUSIONS: In our cohort of patients with LCA, coding sequence variations were observed in the CRB1 gene more frequently than in any of the other 5 known LCA-associated genes. Likely disease-causing sequence variations have now been identified in 64 (28%) of 233 subjects in this cohort. CLINICAL RELEVANCE: Molecular diagnosis can confirm and clarify the diagnosis in an increasing fraction of patients with LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations may be established. This will facilitate the counseling of patients regarding their visual prognosis and the likelihood of associated systemic anomalies.

Adolescent↗

PubMed2001

Novel frameshift mutations in CRX associated with Leber congenital amaurosis.

Mutations in CRX, a photoreceptor-specific transcription factor, can cause Leber congenital amaurosis (LCA), cone-rod dystrophy (CORD), and retinitis pigmentosa (RP), all of which feature severe visual impairment. Upon screening 55 patients with Leber congenital amaurosis, 75 patients with cone-rod dystrophy, 13 with cone dystrophy, and 36 with recessive or isolate RP for changes in the CRX sequence, we found two patients with Leber congenital amaurosis who carried heterozygously one of two novel frameshift mutations. The first mutation, Tyr191(1-bp del), was a de novo change and the second change, Pro263(1-bp del) was inherited from the proband's affected father. Both mutations are predicted to encode mutant versions of CRX with altered carboxy termini. We also found a previously reported missense mutation, Arg41Gln, heterozygously in a 47-year-old patient with a form of RP. The missense change Val242Met was found in an isolate case of CORD and no controls; however, its pathogenicity remains uncertain because only limited segregation analysis was possible. A nonpathogenic missense change, Ala158Thr, was found to be a variant present at relatively high frequency among African-Americans.

DNA↗

PubMed2001

Retinal findings in melanoma-associated retinopathy.

PURPOSE: To report unusual fundus findings in two cases of melanoma-associated retinopathy. METHODS: Observational case reports. The histories of two patients with melanoma-associated retinopathy were reviewed. Sera from both patients were examined for antibodies against retinal bipolar cells. Immunofluorescence was performed on cryostat sections of unfixed normal human retinas. Sera and IgG from both patients were tested against a known melanoma-associated retinopathy patient as well as a control subject. RESULTS: Our patients had metastatic, cutaneous melanoma and a clinical syndrome consistent with melanoma-associated retinopathy. Both patients had serum antibodies that were reactive against retinal bipolar cells. They had unusual fundus changes not previously described in association with melanoma-associated retinopathy. One patient also developed vitiligo. CONCLUSION: Patients with metastatic cutaneous melanoma and melanoma-associated retinopathy may present unusual fundus lesions that may be caused by autoimmunity which is part of the clinical picture of melanoma-associated retinopathy or metastatic melanoma.

Autoantibodies↗

PubMed2001

Contrast discrimination deficits in retinitis pigmentosa are greater for stimuli that favor the magnocellular pathway.

Luminance contrast discrimination was measured in 14 patients with retinitis pigmentosa (RP) and 14 control observers with normal vision, using steady-pedestal and pulsed-pedestal paradigms [Pokorny, J., & Smith, V. C. (1997). Psychophysical signatures associated with magnocellular and parvocellular pathway contrast gain. Journal of the Optical Society of America A, 14, 2477-2486] to bias performance toward the magnocellular (MC) or parvocellular (PC) pathway, respectively. The aim was to determine the relative effects of retinal degeneration on MC- and PC-pathway function in RP. For five of the RP patients, contrast discrimination thresholds were within normal limits for both the steady-pedestal and pulsed-pedestal paradigms. The other nine RP patients showed threshold elevations for the steady-pedestal paradigm (presumed magnocellular mediation), whereas their thresholds for the pulsed-pedestal paradigm (presumed parvocellular mediation) were within normal limits for all but the two patients who had the most extreme threshold elevations using the steady-pedestal paradigm. A control experiment on four of the RP patients, using a greater number of pedestal contrasts, verified that the patients' thresholds for the pulsed-pedestal paradigm showed the pattern expected for contrast discrimination mediated by the PC pathway. The higher threshold elevations for the steady-pedestal paradigm than for the pulsed-pedestal paradigm indicate that the retinal degeneration that occurs in RP predominantly disrupts contrast discrimination under stimulus conditions that favor the MC pathway.

Adult↗

PubMed2001

Perceived and actual performance of daily tasks: relationship to visual function tests in individuals with retinitis pigmentosa.

PURPOSE: To investigate the functioning in daily task performance of individuals with retinitis pigmentosa (RP). Goals were (1) to quantify the relationships among clinical tests of vision, self-reports, and evaluations of actual task performance to predict difficulty in these tasks; and (2) to validate self-report questionnaire data about daily task performance with observations and measurements of actual task performance conducted by a certified low-vision specialist. DESIGN: A cross-sectional study and survey. PARTICIPANTS: Sixty-two individuals with RP (mean age, 37 years) participated in the study. METHODS: We obtained data about task performance from subjects' reports about their daily performance as assessed by a 53-item questionnaire and from a specialist's rating about actual ability on a 64-item battery of tasks, including ones similar to those assessed with the questionnaire. MAIN OUTCOME MEASURES: Clinical measures of vision included visual acuity, visual fields using Goldmann perimetry, letter contrast sensitivity, and cone and rod electroretinogram (ERG) function. The questionnaire and functional tasks were clustered into three categories: "reading," "mobility," and "peripheral detection." RESULTS: Self-report was correlated significantly with actual task performance. Task performance was correlated significantly with clinical test performance. Moderate or worse difficulty in performance was observed only for visual acuity worse than 20/40; log contrast sensitivity less than 1.4; a visual field area smaller than 2000 deg(2) (area equivalent to a 50-degree diameter of visual field to the Goldmann II-4-e target); and ERG amplitudes less than 10 microvolts for 32-Hz light-adapted white flicker. CONCLUSIONS: Despite the significant correlations, there remains variability in task performance that is unaccounted for in some individuals with low levels of clinical test performance. The assessment of actual task performance validated the use of self-reports in individuals with RP.

Activities of Daily Living↗

PubMed2001

Retrospective longitudinal study of visual acuity change in patients with retinitis pigmentosa.

PURPOSE: To determine the extent that clinically evident macular lesions in patients with retinitis pigmentosa (RP) help to establish their prognosis for visual acuity (VA) retention. METHODS: The records of 182 patients with RP were reviewed. The macular lesion status at the initial examination was determined to be no lesion, a bull's-eye atrophic lesion, or a geographic atrophic lesion. Multiple linear regression analysis was used to evaluate the relationship of initial VA, macular lesion type, and RP genetic subtype to predict the VA change per 5-year period. RESULTS: The regression effect of lesion type on the VA change was statistically significant (P < 0.0001). Patients with no macular lesion had a predicted 5-year change of less than 1 line, whereas those with either a bull's-eye or geographic atrophic lesion had a predicted 5-year change of three to four lines. The 5-year changes were not related to a patient's age or level of VA at initial presentation, when controlling for type of macular lesion. CONCLUSION: By examining longitudinal data, the authors found that the presence or absence of a macular lesion at the patient's initial visit was an important determinant of VA loss in this cohort of patients with RP. These findings are of value when counseling patients with RP regarding their prognosis for preservation of VA.

Adolescent↗

PubMed2001

Origin of deficits in the flicker electroretinogram of the cone system in X-linked retinoschisis as derived from response nonlinearities.

The aim of this study was to identify the origin of a high-frequency attenuation in the flicker electroretinogram (ERG) of patients with X-linked retinoschisis (XLRS) through an analysis of nonlinearities in the ERG response. The ERGs of six patients with XLRS and six age-similar control subjects were recorded in response to stimuli that consisted of pairs of sinusoids that had varying temporal frequencies and that differed by either 8 or 16 Hz. Compared with the control subjects, the patients with XLRS showed a significant reduction in the amplitude of the difference frequency to high-frequency stimuli that paralleled the high-frequency attenuation of their ERG response fundamental. This result indicates that a response attenuation at an initial linear filter, most likely photoreceptoral, was a major determinant of the reduced ERG amplitude of the XLRS patients at high temporal frequencies. Additional analyses of nonlinearities in the ERG responses provided evidence of a postreceptoral component to the flicker ERG deficits of the XLRS patients, as well.

Adult↗

PubMed2001

On-response deficit in the electroretinogram of the cone system in X-linked retinoschisis.

PURPOSE: The purpose of this study was to evaluate the hypothesis that the reduced b-wave to a-wave ratio of the brief-flash electroretinogram (ERG) of the cone system typically observed in X-linked retinoschisis (XLRS) represents a relatively greater deficit in the ON response (response to light onset) than the OFF response (response to light offset). A second purpose was to investigate the use of sawtooth flicker as a stimulus for eliciting ERG ON and OFF responses. METHODS: Light-adapted, full-field ERGs were recorded in six patients with XLRS and six age-similar control subjects in response to 8-Hz rapid-on and rapid-off sawtooth flicker to emphasize ON and OFF responses, respectively. ERG responses were analyzed in terms of the amplitudes and implicit times of the a-wave, b-wave, and d-wave components. RESULTS: There was no significant difference between the patients with XLRS and the control subjects for either the amplitude of the a-wave of the ON response or the amplitude of the d-wave of the OFF response. However, the amplitude of the b-wave of the ON response was reduced significantly in the patients with XLRS, resulting in a significantly reduced b-wave to d-wave ratio. The patients' implicit times were increased significantly for all waveform components. CONCLUSIONS: The reduced b-wave to d-wave ratio of the ERG of the cone system in these patients with XLRS is consistent with a relative dysfunction of the cone ON bipolar cell pathway in this disorder. The results show further that sawtooth flicker is a promising stimulus for eliciting well-defined ERG waveforms that can provide a quantitative assessment of the properties of ON and OFF responses in retinal disease.

Adaptation, Ocular↗

PubMed2001

An analysis of allelic variation in the ABCA4 gene.

PURPOSE: To assess the allelic variation of the ATP-binding transporter protein (ABCA4). METHODS: A combination of single-strand conformation polymorphism (SSCP) and automated DNA sequencing was used to systematically screen this gene for sequence variations in 374 unrelated probands with a clinical diagnosis of Stargardt disease, 182 patients with age-related macular degeneration (AMD), and 96 normal subjects. RESULTS: There was no significant difference in the proportion of any single variant or class of variant between the control and AMD groups. In contrast, truncating variants, amino acid substitutions, synonymous codon changes, and intronic variants were significantly enriched in patients with Stargardt disease when compared with their presence in subjects without Stargardt disease (Kruskal-Wallis P < 0.0001 for each variant group). Overall, there were 2480 instances of 213 different variants in the ABCA4 gene, including 589 instances of 97 amino acid substitutions, and 45 instances of 33 truncating variants. CONCLUSIONS: Of the 97 amino acid substitutions, 11 occurred at a frequency that made them unlikely to be high-penetrance recessive disease-causing variants (HPRDCV). After accounting for variants in cis, one or more changes that were compatible with HPRDCV were found on 35% of all Stargardt-associated alleles overall. The nucleotide diversity of the ABCA4 coding region, a collective measure of the number and prevalence of polymorphic sites in a region of DNA, was found to be 1.28, a value that is 9 to 400 times greater than that of two other macular disease genes that were examined in a similar fashion (VMD2 and EFEMP1).

ATP-Binding Cassette Transporters↗

PubMed2001

High-frequency attenuation of the cone ERG and ON-response deficits in X-linked retinoschisis.

PURPOSE: Individuals with X-linked retinoschisis (XLRS) show a comparatively greater reduction of the ON response than the OFF response of the electroretinogram (ERG) of the cone system. At high temporal frequencies, they also show a marked attenuation of the flicker ERG that has been attributed to an abnormal cone photoreceptor response. The purpose of this study was to determine whether the high-frequency response attenuation contributes to the abnormal ERG ON response in XLRS. METHODS: Light-adapted ERGs were recorded from three patients with XLRS and from three control subjects, by using rapid-on and rapid-off sawtooth flicker to emphasize ON and OFF responses, respectively, and by using low-pass sawtooth flicker, from which the high temporal frequencies had been removed to mimic the high-frequency attenuation in XLRS. RESULTS: For the control subjects, removing the high stimulus frequencies reduced the amplitude of the b-wave component of the ON response but had little effect on the amplitude of the d-wave component of the OFF response. In the patients with XLRS, the b-wave component of the ON response was already diminished using the full sawtooth stimulus, and removing the higher stimulus frequencies had no further effect. Patients' ERG responses to the 16-Hz stimulus fundamental alone were also abnormal, in that an initial response component normally present in the ERG was absent. CONCLUSIONS: The overall pattern of findings indicates that two factors contribute to the preferential ON-response deficit in XLRS: first, a high-frequency attenuation of the cone photoreceptor response that effectively produces a low-pass stimulus for the postreceptoral pathway and that affects the ON response more than the OFF response and, second, a relatively greater attenuation of the ON- than of the OFF-bipolar cell response that is evident in the aberrant response to the sawtooth fundamental.

Adaptation, Ocular↗

PubMed2001

CORD9 a new locus for arCRD: mapping to 8p11, estimation of frequency, evaluation of a candidate gene.

PURPOSE: To determine the locus of the mutant gene causing autosomal recessive cone-rod dystrophy (arCRD) in a consanguineous pedigree, to evaluate a candidate gene expressed in retina that maps to this locus, and to estimate the percentage of arCRD cases caused by mutations in this gene. METHODS: DNAs from family members were genotyped for markers covering the entire genome at an average spacing of approximately 9 centimorgans (cM). The data were input into a pedigree computer program to produce output files used to calculate lod scores. Significant linkage was revealed at 8cen, prompting the genotyping of a number of additional markers. Exons of a candidate gene were sequenced directly by standard fluorescent dideoxy methods. Haplotype analysis was performed with markers in this locus in 13 multiplex and 2 simplex CRD families in which neither parent had disease. RESULTS: Four-point linkage analysis gave a maximum lod score of approximately 7.6 at both D8S1769 and GATA101H09 in the large consanguineous family. Recombination events defined an interval of 8.7 cM between D8S1820 and D8S532 within which the gene must lie. This 8p11 locus (CORD9) is immediately distal to but distinct from the RP1 autosomal dominant RP (adRP) locus. Two islands of homozygosity were found in this locus: The alleles of 6 of 10 markers in one of the islands and 2 of 4 in the other were homozygous. The UniGene cluster Hs.8719 (UniGene System, provided by the National Center for Biotechnology Information and available at http://www.ncbi.nlm.nih.gov/UniGene), which tags a gene with significant homology to Dual Specificity Phosphatase 3, maps within the CORD9 interval and is highly expressed in the retina. To evaluate this gene as a potential disease candidate, intron-exon structure was determined, and exons were screened in the consanguineous family. No variants were found that could be related to disease. Haplotype analysis of 15 other families with CRD, using markers at CORD9, excluded this locus in 9 of 15. CONCLUSIONS: A new arCRD locus (CORD9) has been identified corresponding to a yet unidentified gene in the 8.7-cM interval D8S1820-D8S532. No mutations were found in one candidate gene in affected members of the primary study family. Haplotype analysis of a cohort of 13 multiplex and 2 simplex families with CRD ruled out the CORD9 gene in 9 of 15 of the families. To date, a total of 126 loci carrying gene mutations causing various forms of retinal degeneration have been mapped, and the mutant gene has been identified in 64 of them. However, only 2 loci for arCRD have been documented. This is the report of a third.

Chromosome Mapping↗

PubMed2000

Mutation analysis of 3 genes in patients with Leber congenital amaurosis.

OBJECTIVE: To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA). PATIENTS: One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India. METHODS: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) known to be associated with LCA. RESULTS: Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patients who harbored mutations in these genes had associated systemic abnormalities. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA. CONCLUSIONS: Molecular diagnosis may be of benefit to patients affected with LCA. The relative paucity of mutations found in this study suggests that more LCA-associated genes remain to be discovered. CLINICAL RELEVANCE: Molecular diagnosis can confirm and clarify the diagnosis of LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations will be established. This will facilitate the counseling of patients on their visual prognosis and the likelihood of associated systemic anomalies.

Adolescent↗

PubMed2000

Temporal frequency deficits in the electroretinogram of the cone system in X-linked retinoschisis.

We investigated the extent of, and basis for, abnormalities in the flicker electroretinogram (ERG) of the cone system of patients with X-linked retinoschisis (XLRS), a form of hereditary vitreoretinal degeneration. ERGs were recorded from six patients with XLRS and from six visually normal subjects using high-contrast sinusoidal flicker that ranged in temporal frequency from 8 to 96 Hz, and that was presented against a rod-desensitizing adapting field. Compared to the control subjects, the patients with XLRS showed a significant reduction in the amplitude of the ERG response fundamental at temporal frequencies of 32 Hz and higher. In addition, their response phases were at or below the lower limits of normal (representing a phase lag) for temporal frequencies greater than 8 Hz. The higher harmonics of the patients' ERG responses to a low frequency stimulus were attenuated over the same temporal frequency range as was the response fundamental. This finding indicates that a major component of the abnormal temporal filtering responsible for the ERG abnormalities in XLRS occurs beyond the level of the early retinal nonlinearity that generates the harmonic components of the ERG response, and therefore is most likely postreceptoral in origin. Consistent with this interpretation, the ERG waveforms of the XLRS patients showed a significant attenuation of the ON-response component, with a normal OFF response. The overall pattern of results suggests that the marked reduction of ERG response amplitudes and the phase lag at the higher temporal frequencies in XLRS stem, at least in part, from a predominant attenuation of the ON-bipolar cell contribution to the flicker ERG.

Adolescent↗

PubMed2000

A longitudinal study of visual function in carriers of X-linked recessive retinitis pigmentosa.

OBJECTIVE: This study was carried out to evaluate the progression of visual function impairment in carriers of X-linked recessive retinitis pigmentosa. We also assessed the relationship between the retinal findings at presentation and the extent of deterioration. DESIGN: Observational, retrospective, case series. PARTICIPANTS: Twenty-seven carriers of X-linked recessive retinitis pigmentosa. METHODS: Each carrier was clinically categorized into one of four grades (grades 0 through 3) depending on the presence or absence of a tapetal-like retinal reflex and the extent of peripheral pigmentary degeneration. A complete ophthalmologic examination was performed and data for visual acuity, visual field area, and electroretinographic measurements were collected on the most recent visit in both eyes. These were then compared with similar data obtained on their initial visits. MAIN OUTCOME MEASURES: A comparison of visual function was carried out between the initial visit and the most recent visit on each carrier. The visual acuity was measured with Snellen's acuity charts. The visual fields to targets V-4-e and II-4-e were planimeterized and used for the analysis. The electroretinographic (ERG) measures used were light-adapted single-flash b-wave amplitudes and 30-Hz red flicker for cone function, dark-adapted maximal b-wave amplitudes, and response to a low intensity blue-flash for rod function. RESULTS: None of the 11 carriers with a tapetal-like reflex only (grade 1) showed any significant change in visual acuity or fields as compared with 3 of 7 (43%) carriers with diffuse peripheral pigmentary findings (grade 3) who showed significant deterioration in visual acuity in at least one eye, and 6 of 7 (86%) who showed a significant decrease in visual field area with at least one target size in at least one eye. By comparison, only 1 of 10 carriers with a grade 1 fundus finding demonstrated a significant decrease in maximal dark-adapted ERG function as compared with 5 of 6 (83%) carriers with grade 3 in response to a single-flash stimulus and with 4 of 5 (80%) carriers in response to a single-flash blue stimulus. For the single-flash photopic response, none of the 10 carriers with grade 1 showed any significant deterioration, whereas 2 of 4 (50%) with grade 3 did show such deterioration. The ERG responses for carriers with grade 2 were in between the extent of decrease in ERG amplitudes of those in carriers with grades 1 and 3. CONCLUSIONS: In our cohort of X-linked retinitis pigmentosa carriers, those with only a tapetal-like retinal reflex at presentation had a better prognosis to retain visual function than those with peripheral retinal pigmentation. These data are useful in counseling such carriers as to their visual prognosis.

Adolescent↗

PubMed2000

Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate.

Hereditary human retinal degenerative diseases usually affect the mature photoreceptor topography by reducing the number of cells through apoptosis, resulting in loss of visual function. Only one inherited retinal disease, the enhanced S-cone syndrome (ESCS), manifests a gain in function of photoreceptors. ESCS is an autosomal recessive retinopathy in which patients have an increased sensitivity to blue light; perception of blue light is mediated by what is normally the least populous cone photoreceptor subtype, the S (short wavelength, blue) cones. People with ESCS also suffer visual loss, with night blindness occurring from early in life, varying degrees of L (long, red)- and M (middle, green)-cone vision, and retinal degeneration. The altered ratio of S- to L/M-cone photoreceptor sensitivity in ESCS may be due to abnormal cone cell fate determination during retinal development. In 94% of a cohort of ESCS probands we found mutations in NR2E3 (also known as PNR), which encodes a retinal nuclear receptor recently discovered to be a ligand-dependent transcription factor. Expression of NR2E3 was limited to the outer nuclear layer of the human retina. Our results suggest that NR2E3 has a role in determining photoreceptor phenotype during human retinogenesis.

Amino Acid Sequence↗