161 results on '"Maumenee I"'
Search Results
2. Assignment of the Nance-Horan syndrome to the distal short arm of the X chromosome
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Zhu, D., Alcorn, D. M., Antonarakis, S. E., Levin, L. S., Huang, P. C., Mitchell, T. N., Warren, A. C., and Maumenee, I. H.
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- 1990
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3. Cherry red spot in association with galactosylceramide-β-galactosidase deficiency
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Hofman, K. J., Naidu, S., Moser, H. W., Maumenee, I. H., and Wenger, D. A.
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- 1987
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4. A G1103R Mutation in CRB1 is Co-Inherited with High Hyperopia and Leber Congenital Amaurosis.
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Abouzeid, H., Li, Y., Maumenee, I. H., Dharmaraj, S., and Sundin, O.
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BLINDNESS ,HYPEROPIA ,EXONS (Genetics) ,DNA ,GENETIC mutation ,GENES - Abstract
Purpose: To identify the genetic basis of recessive inheritance of high hyperopia and Leber congenital amaurosis (LCA) in a family of Middle Eastern origin. Materials and methods: The patients were examined using standard ophthalmic techniques. DNA samples were obtained and genetic linkage was carried out using polymorphic markers flanking the known genes and loci for LCA. Exons were amplified and sequenced. Results: All four members of this family affected by LCA showed high to extreme hyperopia, with average spherical refractive errors ranging from +5.00 to +10.00. Linkage was obtained to 1q31.3 with a maximal LOD score of 5.20 and a mutation found in exon 9 of the CRB1 gene, causing a G1103R substitution at a highly conserved site in the protein. CRB1 is a vertebrate homolog of the Drosophila crumbs gene, which is required for photoreceptor morphogenesis, and has been associated with either retinitis pigmentosa (RP) or LCA. This sequence variant has previously been reported as a compound heterozygote in one sporadic LCA patient. Conclusion: Although hyperopia has been associated with LCA, it is typically moderate and variable between patients with the same mutation. In addition, some CRB1 mutations can be associated with either RP or LCA. We have shown that hyperopia and LCA are linked to the mutant CRB1 gene itself and are not dependent on unlinked modifiers. [ABSTRACT FROM AUTHOR]
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- 2006
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5. Ocular ultrastructural studies of two cases of the Hurler syndrome (systemic mucopolysaccharidosis I-H).
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Chao Chan, Chi, Richard Green, W., Maumenee, I. H., and Sack, George H.
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- 1983
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6. Prevalence of map-dot-fingerprint changes in the cornea.
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Werblin, T P, Hirst, L W, Stark, W J, and Maumenee, I H
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Map-dot-fingerprint basement-membrane abnormalities of the cornea are common in the general population, affecting as many as 76% of persons over age 50 and 42% of persons of all ages. The prevalence of this condition in the general population is not significantly different from that found in families of patients with recurrent corneal erosions and map-dot-fingerprint corneal changes. Despite this extremely high prevalence of basement-membrane changes the incidence of recurrent erosive symptoms in total groups of patients with basement-membrane changes is quite rare, suggesting that these 2 entities are possibly not related. Although previous observers have suggested an autosomal dominant mode of inheritance of these basement-membrane changes, our data raise the possibility that map-dot-fingerprint basement-membrane changes represent an age-dependent, degenerative condition of the cornea. We were unable, however, to prove either hypothesis. [ABSTRACT FROM PUBLISHER]
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- 1981
7. A patterned macular dystrophy with yellow plaques and atrophic changes.
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Cortin, P, Archer, D, Maumenee, I H, Feiock, K, and Speros, P
- Abstract
Three middle-aged male patients are described with a peculiar patterned dystrophy of the macula. The basic lesions are discrete yellow plaques typically confined to the macular area and radiating from the fovea. They appear to be located at the level of the retinal pigment epithelium (RPE). With the passage of time some of the yellow plaques altered in extent and configuration, and atrophic changes appeared or extended. Visual acuity and electrophysiological tests are either normal or only moderately affected. The lesions appear to be distinct from the patterned dystrophies of the retina already described and from other conditions characterised by yellow or white deposits at the level of the RPE. [ABSTRACT FROM PUBLISHER]
- Published
- 1980
8. Value of combined phenotypic markers in identifying inheritance of familial adenomatous polyposis.
- Author
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Giardiello, F M, Offerhaus, G J, Traboulsi, E I, Graybeal, J C, Maumenee, I H, Krush, A J, Levin, L S, Booker, S V, and Hamilton, S R
- Abstract
Familial adenomatous polyposis is an autosomal dominant disease characterised by the development of hundreds of colorectal adenomas in young adults. Occult radio-opaque jaw lesions and pigmented ocular fundus lesions (formerly called congenital hypertrophy of the retinal pigment epithelium) are extraintestinal phenotypic markers for this disorder. We evaluated the usefulness of the combination of these markers for identifying patients who have inherited familial adenomatous polyposis. Forty three affected patients and 12 unaffected first degree relatives from 24 families with familial adenomatous polyposis, including four families without extraintestinal manifestations, were examined for both phenotypic markers. Thirty three of the 43 patients (77%) with familial adenomatous polyposis were positive for both markers, including patients from two families without extraintestinal manifestations. By contrast, only one of 12 (8%) unaffected first degree relatives over 35 years of age had both markers. The sensitivity of the combination of these markers in identifying patients who inherited familial adenomatous polyposis was 77%, the specificity 92%, the predictive value of a positive test 97%, the predictive value of a negative test 52%, and the efficacy 80%. The combined markers had improved efficacy over either marker alone (70% for occult radio-opaque jaw lesions and 67% for pigmented ocular fundus lesions). We conclude that the presence of both occult radio-opaque jaw lesions and pigmented ocular fundus lesions in a person at risk indicates a high probability of inheritance and expression of familial adenomatous polyposis. [ABSTRACT FROM PUBLISHER]
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- 1991
9. Neuro-ophthalmic genetics.
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Kerrison, J B and Maumenee, I H
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- 1997
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10. Assessment of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene localised to 6q13-q15 in autosomal dominant Stargardt-like disease (ADSTGD), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1).
- Author
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Gehrig, A, Felbor, U, Kelsell, R E, Hunt, D M, Maumenee, I H, and Weber, B H
- Abstract
We have recently characterised the genomic organisation of a novel interphotoreceptor matrix proteoglycan, IMPG1, and have mapped the gene locus to chromosome 6q13-q15 by fluorescence in situ hybridisation. As the interphotoreceptor matrix (IPM) is thought to play a critical role in retinal adhesion and the maintenance of photoreceptor cells, it is conceivable that a defect in one of the IPM components may cause degenerative lesions in retinal structures and thus may be associated with human retinopathies. By genetic linkage analysis, several retinal dystrophies including one form of autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1) have previously been localised to a region on proximal 6q that overlaps the IMPG1 locus. We have therefore assessed the entire coding region of IMPG1 by exon amplification and subsequent single stranded conformational analysis in patients from 6q linked multigeneration families diagnosed with PBCRA and MCDR1, as well as a single patient from an autosomal dominant STGD pedigree unlinked to either of the two known STGD2 and STGD3 loci on chromosomes 13q and 6q, respectively. No disease associated mutations were identified. In addition, using an intragenic polymorphism, IMPG1 was excluded by genetic recombination from both the PBCRA and the MCDR1 loci. However, as the autosomal dominant Stargardt-like macular dystrophies are genetically heterogeneous, other forms of this disorder, in particular STGD3 previously linked to 6q, may be caused by mutations in IMPG1. [ABSTRACT FROM PUBLISHER]
- Published
- 1998
11. Bilateral symmetry of vision disorders in typical retinitis pigmentosa.
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Massof, R W, Finkelstein, D, Starr, S J, Kenyon, K R, Fleischman, J A, and Maumenee, I H
- Abstract
Bilateral symmetry of disorders of vision is examined in 60 typical patients with retinitis pigmentosa. We observed a very high degree of interocular congruence in the patterns of both kinetic visual field defects and threshold profiles and in abnormalities of foveal colour discrimination and visual acuity. Abnormalities of foveal colour vision are highly correlated with the extent of visual field loss. [ABSTRACT FROM PUBLISHER]
- Published
- 1979
12. Olivopontocerebellar Atrophy with Retinal Degeneration.
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Traboulsi, E I, Maumenee, I H, Green, W R, Freimer, M L, and Moser, H.
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- 1989
13. Leber's Congenital Amaurosis.
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Schroeder, R, Mets, M B, Maumenee, I H, and Mets, M. B.
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- 1987
14. Extraocular Muscle Aplasia in Moebius Syndrome.
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Jay, Walter M., Traboulsi, E I, and Maumenee, I H
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- 1986
15. GENETIC EYE DISEASES.
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Cotlier, E., Maumenee, I. H., and Berman, E. R.
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- 1987
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16. Re: Patel et al.: The Oculome Panel Test: next-generation sequencing to diagnose a diverse range of genetic developmental eye disorders (Ophthalmology. 2019;126:888-907).
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Bateman B and Maumenee I
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- Child, Developmental Disabilities, Humans, Eye Diseases, High-Throughput Nucleotide Sequencing
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- 2020
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17. An unbalanced translocation between chromosomes 2p and 6p associated with Axenfeld-Rieger anomaly type 3, hearing loss, developmental delay, and distinct facial dysmorphism.
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Li F, Batista DA, Maumenee I, and Wang T
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- Adolescent, Chromosome Aberrations, Chromosome Banding, Comparative Genomic Hybridization, Humans, Male, Abnormalities, Multiple genetics, Chromosomes, Human, Pair 2 genetics, Chromosomes, Human, Pair 6 genetics, Developmental Disabilities genetics, Face abnormalities, Hearing Loss genetics, Translocation, Genetic
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- 2010
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18. Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles.
- Author
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Zernant J, Külm M, Dharmaraj S, den Hollander AI, Perrault I, Preising MN, Lorenz B, Kaplan J, Cremers FP, Maumenee I, Koenekoop RK, and Allikmets R
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- Blindness congenital, DNA Mutational Analysis, Female, Gene Expression Profiling, Genetic Testing, Genetic Variation, Genotype, Humans, Infant, Male, Pedigree, Polymerase Chain Reaction, Retinal Degeneration congenital, Alleles, Blindness genetics, Mutation, Oligonucleotide Array Sequence Analysis, Retinal Degeneration genetics
- Abstract
Purpose: Leber congenital amaurosis (LCA) is an early-onset inherited disorder of childhood blindness characterized by visual impairment noted soon after birth. Variants in at least six genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1) have been associated with a diagnosis consistent with LCA or early-onset retinitis pigmentosa (RP). Genetically heterogeneous inheritance complicates the analyses of LCA cases, especially in patients without a family history of the disorder, and conventional methods are of limited value., Methods: To overcome these limitations, arrayed primer extension (APEX) technology was used to design a genotyping microarray for early-onset, severe retinal degenerations that includes all of the >300 disease-associated variants currently described in eight genes (in addition to the six just listed, the early-onset RP genes LRAT and MERTK were added). The resultant LCA array allows simultaneous detection of all known disease-associated alleles in any patient with early-onset RP. The array was validated by screening 93 confirmed patients with LCA who had known mutations. Subsequently, 205 novel LCA cases were screened on the array, followed by segregation analyses in families, if applicable., Results: The microarray was >99% effective in determining the existing genetic variation and yielded at least one disease-associated allele in approximately one third of the novel patients. More than two (expected) variants were discovered in a substantial fraction (22/300) of the patients, suggesting a modifier effect from more than one gene. In support of the latter hypothesis, the third allele segregated with a more severe disease phenotype in at least five families., Conclusions: The LCA genotyping microarray is a robust and cost-effective screening tool, representing the prototype of a disease chip for genotyping patients with a genetically heterogeneous condition. Simultaneous screening for all known LCA-associated variants in large LCA cohorts allows systematic detection and analysis of genetic variation, facilitating prospective diagnosis and ultimately predicting disease progression.
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- 2005
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19. A missense mutation in GUCY2D acts as a genetic modifier in RPE65-related Leber Congenital Amaurosis.
- Author
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Silva E, Dharmaraj S, Li YY, Pina AL, Carter RC, Loyer M, Traboulsi E, Theodossiadis G, Koenekoop R, Sundin O, and Maumenee I
- Subjects
- Adult, Blindness congenital, Carrier Proteins, Chromosome Segregation, Eye Proteins, Female, Genotype, Homozygote, Humans, Pedigree, Phenotype, Retinal Degeneration congenital, Siblings, cis-trans-Isomerases, Blindness genetics, Guanylate Cyclase genetics, Mutation, Missense genetics, Proteins genetics, Receptors, Cell Surface genetics, Retinal Degeneration genetics
- Abstract
Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous severe retinal dystrophy presenting in infancy. To explain the phenotypical variability observed in two affected siblings of a consanguineous pedigree diagnosed with LCA and establish a genotype-phenotype correlation, we screened GUCY2D, RPE65, CRX, AIPL1, and RPGRIP1 for mutations. The more severely affected sibling carried a heterozygous missense mutation in the GUCY2D gene (Ile539Val), which did not segregate with the disease phenotype. Subsequently, a homozygous nonsense mutation (Glu102STOP) in the RPE65 gene was identified in both affected siblings, thus identifying the causative gene. This data provides evidence for the presence of genetic modulation in LCA. It appears that the heterozygous GUCY2D mutation further disrupts the already compromised photoreceptor function resulting in more severe retinal dysfunction in the older sibling. We suggest that the unusual phenotypic variability in these two siblings with LCA is caused by the modifying effect of a heterozygous GUCY2D mutation observed against the disease background of a homozygous RPE65 mutation.
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- 2004
- Full Text
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20. Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy.
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Baris O, Delettre C, Amati-Bonneau P, Surget MO, Charlin JF, Catier A, Derieux L, Guyomard JL, Dollfus H, Jonveaux P, Ayuso C, Maumenee I, Lorenz B, Mohammed S, Tourmen Y, Bonneau D, Malthièry Y, Hamel C, and Reynier P
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- Alternative Splicing, Codon, Nonsense, DNA chemistry, DNA genetics, DNA Mutational Analysis, Humans, Mutagenesis, Insertional, Mutation, Missense, Optic Atrophy enzymology, Optic Atrophy pathology, Optic Atrophy, Autosomal Dominant enzymology, Optic Atrophy, Autosomal Dominant pathology, Phenotype, Sequence Deletion, GTP Phosphohydrolases genetics, Mutation, Optic Atrophy genetics, Optic Atrophy, Autosomal Dominant genetics
- Abstract
The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy., (Copyright 2003 Wiley-Liss, Inc.)
- Published
- 2003
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21. Identification of GUCY2D gene mutations in CORD5 families and evidence of incomplete penetrance.
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Udar N, Yelchits S, Chalukya M, Yellore V, Nusinowitz S, Silva-Garcia R, Vrabec T, Hussles Maumenee I, Donoso L, and Small KW
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- Adolescent, Adult, Amino Acid Sequence, Amino Acid Substitution genetics, Animals, Arginine genetics, Cattle, Child, Child, Preschool, Dogs, Echinacea genetics, Female, Genes, Dominant genetics, Genetic Markers genetics, Histidine genetics, Humans, Male, Mice, Middle Aged, Molecular Sequence Data, Pedigree, Plant Proteins genetics, Rats, Recombination, Genetic genetics, Guanylate Cyclase genetics, Mutation genetics, Optic Atrophies, Hereditary enzymology, Optic Atrophies, Hereditary genetics, Penetrance
- Abstract
Cone rod dystrophy 5 (CORD5) is an autosomal dominant retinal disease that primarily affects cone function. The locus has previously been mapped to human chromosome 17p12-p13 between the markers D17S926/D17S849 and D17S945/D17S804. One of our "unaffected" recombinant individual from family 1175 was subsequently found to cross through this interval. Reexamination revealed that he was in fact mildly affected. This expanded the minimum candidate region. Direct sequencing of the GUCY2D and other candidate genes within this interval was carried out on 2 American families affected with CORD5. There was an R838C missense mutation within the GUCY2D gene in one and a R838H missense mutation in another families. The previously reported mutations for CORD6 are clustered at the same position within the gene. These results indicate that both CORD5 (MIM# 600977) and CORD6 (MIM# 601777) are actually the same disease. We conclude that significant variability in expression and incomplete penetrance exists even within one family., (Copyright 2003 Wiley-Liss, Inc.)
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- 2003
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22. Electroretinographic abnormalities in parents of patients with Leber congenital amaurosis who have heterozygous GUCY2D mutations.
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Koenekoop RK, Fishman GA, Iannaccone A, Ezzeldin H, Ciccarelli ML, Baldi A, Sunness JS, Lotery AJ, Jablonski MM, Pittler SJ, and Maumenee I
- Subjects
- Adaptation, Ocular, Dark Adaptation, Female, Genotype, Humans, Male, Middle Aged, Photic Stimulation methods, Psychophysics methods, Retinal Rod Photoreceptor Cells physiopathology, Retinitis Pigmentosa diagnosis, Retinitis Pigmentosa physiopathology, Sensory Thresholds, Visual Perception, Electroretinography, Heterozygote, Mutation, Parents, Retinitis Pigmentosa congenital, Retinitis Pigmentosa genetics
- Abstract
Background: Leber congenital amaurosis (LCA) is an infrequently encountered congenital form of retinitis pigmentosa with marked genetic and clinical heterogeneity. Thus far, 10 genes have been identified in this disorder since 1996. In the future, LCA may become treatable by gene and/or pharmacological intervention, and these therapies will likely be gene specific, giving major significance to rapid gene identification and gene-phenotype studies., Objective: To test the hypothesis that parents of patients with LCA have identifiable electroretinographic and psychophysical changes. SUBJECTS, MATERIALS, AND METHODS: Complete eye examinations and electroretinographic studies were performed on 2 sets of parents whose offspring were diagnosed as having LCA and who were found to carry a mutation in 1 of the 10 LCA genes-GUCY2D. One set of parents also underwent static perimetry threshold measurements., Results: We found that single flash-light-adapted a- and b-wave amplitudes, 30-Hz flicker, or both cone signals were significantly decreased in amplitude in 4 heterozygotes, while 2 parents showed delayed 30-Hz flicker implicit times. Electroretinographic rod-mediated signals were normal in 2 of the heterozygotes, but subnormal in 2. Static perimetry testing showed normal thresholds in the 2 heterozygotes tested., Main Outcome Measures: Single flash-light-adapted a- and b-wave amplitudes and implicit times, 30- or 32-Hz flicker amplitudes and implicit times, rod-mediated signals, and dark-adapted, rod-mediated thresholds., Conclusions: Some carrier parents of patients with LCA and a GUCY2D mutation develop measurable, cone and possibly rod abnormalities most consistent with a mild cone-rod dysfunction. This correlates well with the known retinal expression pattern of GUCY2D, which is considerably higher in cone compared with rod photoreceptor cells.
- Published
- 2002
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23. Clinical and genetic analysis of a family with X-linked congenital nystagmus (NYS1).
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Kerrison JB, Giorda R, Lenart TD, Drack AV, and Maumenee IH
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- Age of Onset, Chromosome Mapping, DNA analysis, DNA Primers chemistry, Exons, Female, Humans, Lod Score, Male, Microsatellite Repeats, Pedigree, Polymerase Chain Reaction, Visual Acuity, White People, Genetic Linkage, Nystagmus, Congenital genetics, X Chromosome genetics
- Abstract
Purpose: To describe a family with X-linked congenital nystagmus and identify the genetic interval within which the gene is located., Methods and Design: Clinical examination with genotyping of 30 individuals from a multi-generational Caucasian family with congenital nystagmus inherited in an X-linked pattern using markers from Xq26-q27, followed by linkage analysis and sequencing of a candidate gene, solute carrier family 25, member 14 (SLC25A14), in four affected individuals from four families linked to this region., Results: The pattern of inheritance in the family was consistent with X-linkage with incomplete penetrance among carrier females. No affected males had affected sons. Based on the extended pedigree, the estimated penetrance among obligate female carriers (daughters of affected males) was 29% (6 of 21). Visual acuity among 15 affected individuals ranged from 20/20 to 20/70 (median 20/30). Clinical examinations, including electroretinography in two individuals, were otherwise normal except for the presence of nystagmus. Significant LOD scores (theta = 0) were found with markers DXS8057, DXS8044, DXS1047, DXS1062, DXS8072, and DXS8078, placing the gene within a approximately 5 cM interval flanked by DXS9909 and DXS1211 on the long arm of the X chromosome. Sequencing the candidate gene SLC25A14 in four affected individuals from four families linked to this region failed to reveal any mutations., Conclusions: NYS1 appears to be a common gene for familial congenital idiopathic nystagmus. Linkage analysis of this family further reduces the interval in which NYS1 is located.
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- 2001
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24. The ateliotic macula: a newly recognized developmental anomaly.
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De Pool ME, el-Hileli H, and Maumenee IH
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- Adolescent, Child, Preschool, Electroretinography, Eye Abnormalities diagnosis, Eye Abnormalities genetics, Female, Humans, Infant, Infant, Newborn, Male, Phenotype, Refractive Errors diagnosis, Refractive Errors etiology, Refractive Errors genetics, Retinal Diseases diagnosis, Retinal Diseases genetics, Visual Acuity, Eye Abnormalities etiology, Macula Lutea abnormalities, Retinal Diseases etiology
- Abstract
Purpose: We present a macular phenotype resulting from 1 or more abnormalities in the developmental pathway of the central retina., Methods: We describe the clinical and genetic characteristics of 7 patients observed since shortly after birth with regard to visual acuity, refractive error, anterior segment status, retinal findings including foveal structure, and natural history., Results: The patients varied in age from 18 months to 18 years. All patients were examined for the first time during their first year of life and by us at the age of 5 years or younger. The longest follow-up period was 16 years. The abnormal appearance of the macula consisted of thinning of the retina, rarefication of the pigment epithelium with excess visibility of the large choroidal vessels, and absence of the foveal reflex. The visual acuities varied from 20/20 in the better eye to light perception. A retinal detachment was noted in 1 patient at age 2 1/2 years. The refractive errors varied from -2.50 to -16.50 diopters of spherical equivalent. The disease was limited to the retina in 4 patients. In 2 patients, however, developmental abnormalities of the anterior segment were also present; they consisted of malformation of the iris in 1 patient and Peters' anomaly in the other. The electroretinogram (ERG) showed reduced but not absent photopic responses and some reduction in scotopic responses., Conclusion: The phenotype of ateliotic macula is being defined as characterized by an unfinished or primordial appearance. In the 7 patients studied, visual loss was noted shortly after birth. The visual outcome was variable with regard to visual acuity, but many patients showed improvement. There was no evidence of significant worsening of the disease with age except in 1 patient who had a retinal detachment. The ERG responses showed primarily photopic but also scotopic changes. The better-preserved ERG differentiates this disorder from Leber's congenital amaurosis.
- Published
- 2001
25. A case-control study of tobacco and alcohol consumption in Leber hereditary optic neuropathy.
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Kerrison JB, Miller NR, Hsu F, Beaty TH, Maumenee IH, Smith KH, Savino PJ, Stone EM, and Newman NJ
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- Adolescent, Adult, Aged, Child, Female, Humans, Male, Middle Aged, Odds Ratio, Optic Atrophies, Hereditary complications, Optic Atrophies, Hereditary epidemiology, Retrospective Studies, Risk Factors, Self Disclosure, Survival Analysis, United States epidemiology, Alcohol Drinking adverse effects, DNA, Mitochondrial genetics, Optic Atrophies, Hereditary genetics, Point Mutation, Smoking adverse effects, Vision Disorders etiology
- Abstract
Purpose: To determine if tobacco or alcohol consumption is associated with vision loss among sibships harboring pathogenic mitochondrial mutations associated with Leber hereditary optic neuropathy., Methods: Retrospective case-control study with questionnaires obtained from both affected and unaffected siblings from 80 sibships with Leber hereditary optic neuropathy. Sibships harbored molecularly confirmed mitochondrial DNA mutations at nucleotide positions 11778 (63), 14484 (10), and 3460 (7). Exposure in affected individuals was calculated based on reported consumption before vision loss., Results: For male probands (67 sibships), the recurrence risk within a sibship was 10.3% (eight of 78) for males and 3.1% (three of 98) for females. For female probands (13 sibships), the recurrence risk within a sibship was 17.6% (three of 17) for males and 0% (zero of 22) for females. Greater risk of vision loss was associated with male sex (odds ratio [OR] = 6.63; 95% confidence interval [CI] = 2.96 to 14.84; P =.00001) and harboring a 3460 or 14484 in comparison with the 11778 mutation (OR = 2.071; 95% CI = 1.19 to 3.58; P =.0095). No significant association of maximal intensity of smoking or cumulative smoking, whether light or heavy, with vision loss was observed. Light (OR = 0. 31; 95% CI = 0.17 to 0.56; P =.0001) and heavy alcohol consumers (OR = 0.25; 95% CI = 0.11 to 0.58; P =.0011) were less likely to be affected than individuals who did not consume alcohol after adjusting for age, sex, and mutation. In a categorical analysis of sibships with the 3460 or 14484 mutation, no relationship of vision loss with tobacco or alcohol consumption was observed., Conclusion: Unlike previous studies, the present study calculated exposure based on self-reported consumption of tobacco or alcohol before vision loss. No significant deleterious association between tobacco or alcohol consumption and vision loss among individuals harboring Leber hereditary optic neuropathy mutations was observed. Tobacco and alcohol do not appear to promote vision loss in Leber hereditary optic neuropathy.
- Published
- 2000
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26. Mutational analysis and clinical correlation in Leber congenital amaurosis.
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Dharmaraj SR, Silva ER, Pina AL, Li YY, Yang JM, Carter CR, Loyer MK, El-Hilali HK, Traboulsi EK, Sundin OK, Zhu DK, Koenekoop RK, and Maumenee IH
- Subjects
- Adult, Blindness congenital, Blindness diagnosis, Carrier Proteins, Child, Child, Preschool, DNA Mutational Analysis, Female, Follow-Up Studies, Genotype, Humans, Infant, Male, Optic Atrophies, Hereditary diagnosis, Pedigree, Phenotype, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, cis-trans-Isomerases, Blindness genetics, Eye Proteins genetics, Guanylate Cyclase genetics, Homeodomain Proteins genetics, Mutation genetics, Optic Atrophies, Hereditary genetics, Proteins genetics, Trans-Activators genetics
- Abstract
Unlabelled: Leber congenital amaurosis (LCA, MIM 204001) is a clinically and genetically heterogeneous retinal disorder characterized by severe visual loss from birth, nystagmus, poor pupillary reflexes, retinal pigmentary or atrophic changes, and a markedly diminished electroretinogram (ERG)., Purpose: To examine 100 consecutive patients with LCA in order to assess the relative burden of the three known genes involved in LCA, namely retinal guanylyl cyclase (GUCY2D), retinal pigment epithelium protein ( RPE65), and the cone-rod homeobox (CRX), and to define their clinical correlates., Methods: Mutational analysis and detailed clinical examinations were performed in patients diagnosed with LCA at the Johns Hopkins Center for Hereditary Eye Diseases and the Montreal Children's Hospital., Results: Mutations were identified in 11% of our patients: GUCY2D mutations accounted for 6%, while RPE65 and CRX gene mutations accounted for 3% and 2%, respectively. The clinical presentation was variable; however, the visual evolution in patients with mutations in GUCY2D and CRX remained stable, while individuals with mutations in the RPE65 gene showed progressive visual loss., Conclusions: This study suggests that molecular diagnosis of Leber congenital amaurosis could provide important information concerning prognosis and course of treatment.
- Published
- 2000
27. A CRX null mutation is associated with both Leber congenital amaurosis and a normal ocular phenotype.
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Silva E, Yang JM, Li Y, Dharmaraj S, Sundin OH, and Maumenee IH
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- Base Sequence, DNA Mutational Analysis, Humans, Molecular Sequence Data, Pedigree, Phenotype, Blindness genetics, Eye Proteins genetics, Homeodomain Proteins genetics, Mutation, Optic Atrophies, Hereditary genetics, Trans-Activators genetics
- Abstract
Purpose: To identify and characterize new cone rod homeobox (CRX) mutations associated with the Leber congenital amaurosis phenotype., Methods: The human CRX gene was sequenced in 74 consecutive patients carrying the diagnosis of Leber congenital amaurosis., Results: Two mutations were identified in CRX that cause frameshifts and predict severe truncations of the encoded protein. One of these, a 1-bp insertion, spares only nine N-terminal amino acids, removing the homeodomain, WSP motif, and conserved OTX domain at the C terminus. Of the CRX mutations described in the literature, this is the first that convincingly represents a null allele of the gene. Although the patient heterozygous for this null allele is affected with Leber congenital amaurosis, it was surprising that her father, who had normal vision, was heterozygous for the same mutation., Conclusions: These results strongly suggest that haploinsufficiency of CRX is not sufficient to cause a retinal disorder. Loss of function alleles of CRX appear to cause Leber congenital amaurosis through a recessive or multigenic mechanism.
- Published
- 2000
28. Genetic basis of total colourblindness among the Pingelapese islanders.
- Author
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Sundin OH, Yang JM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, and Maumenee IH
- Subjects
- Adolescent, Amino Acid Sequence, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 8, Cyclic Nucleotide-Gated Cation Channels, DNA, Complementary, Female, Genetic Linkage, Humans, Male, Micronesia, Molecular Sequence Data, Pedigree, Polymorphism, Genetic, Color Vision Defects genetics, Ion Channels genetics
- Abstract
Complete achromatopsia is a rare, autosomal recessive disorder characterized by photophobia, low visual acuity, nystagmus and a total inability to distinguish colours. In this disease, cone photoreceptors, the retinal sensory neurons mediating colour vision, seem viable but fail to generate an electrical response to light. Achromatopsia, or rod monochromatism, was first mapped to 2p11-2q12 (MIM 216900; ref. 3), where it is associated with missense mutations in CNGA3 (ref. 4). CNGA3 encodes the alpha-subunit of the cone cyclic nucleotide-gated cation channel, which generates the light-evoked electrical responses of cone photoreceptors. A second locus at 8q21-q22 has been identified among the Pingelapese islanders of Micronesia, who have a high incidence of recessive achromatopsia (MIM 262300). Here we narrow the achromatopsia locus to 1.4 cM and show that Pingelapese achromatopsia segregates with a missense mutation at a highly conserved site in CNGB3, a new gene that encodes the beta-subunit of the cone cyclic nucleotide-gated cation channel. Two independent frameshift deletions establish that achromatopsia is the null phenotype of CNGB3. Combined with earlier findings, our results demonstrate that both alpha- and beta-subunits of the cGMP-gated channel are essential for phototransduction in all three classes of cones.
- Published
- 2000
- Full Text
- View/download PDF
29. Prevalence of AIPL1 mutations in inherited retinal degenerative disease.
- Author
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Sohocki MM, Perrault I, Leroy BP, Payne AM, Dharmaraj S, Bhattacharya SS, Kaplan J, Maumenee IH, Koenekoop R, Meire FM, Birch DG, Heckenlively JR, and Daiger SP
- Subjects
- Adaptor Proteins, Signal Transducing, Blindness genetics, Blindness pathology, DNA Mutational Analysis, DNA Primers chemistry, Exons, Eye Proteins, Female, Humans, Introns, Male, Optic Atrophies, Hereditary genetics, Optic Atrophies, Hereditary pathology, Pedigree, Phenotype, Photoreceptor Cells, Vertebrate pathology, Polymorphism, Single-Stranded Conformational, Prevalence, Retinal Degeneration pathology, Sequence Analysis, DNA, Carrier Proteins genetics, Mutation, Retinal Degeneration genetics
- Abstract
Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy and the most frequent cause of inherited blindness in children. LCA is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. One form of LCA, LCA4, maps to chromosome 17p13 and is genetically distinct from other forms of LCA. We recently identified the gene associated with LCA4, AIPL1 (aryl-hydrocarbon interacting protein-like 1) and identified three mutations that were the cause of blindness in five families with LCA. In this study, AIPL1 was screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases to determine if AIPL1 mutations cause other forms of inherited retinal degeneration and to determine the relative contribution of AIPL1 mutations to inherited retinal disorders in populations worldwide. We identified 11 LCA families whose retinal disorder is caused by homozygous or compound heterozygous AIPL1 mutations. We also identified affected individuals in two apparently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who are heterozygous for a 12-bp AIPL1 deletion. Our results suggest that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy., (Copyright 2000 Academic Press.)
- Published
- 2000
- Full Text
- View/download PDF
30. Microfibril abnormalities of the lens capsule in patients with Marfan syndrome and ectopia lentis.
- Author
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Traboulsi EI, Whittum-Hudson JA, Mir SH, and Maumenee IH
- Subjects
- Adult, Antibodies, Monoclonal, Fibrillins, Humans, Immunoenzyme Techniques, Lens Capsule, Crystalline metabolism, Microfibrils metabolism, Microfilament Proteins metabolism, Middle Aged, Staining and Labeling, Ectopia Lentis pathology, Lens Capsule, Crystalline pathology, Marfan Syndrome pathology, Microfibrils pathology
- Abstract
Purpose: To determine the distribution and structure of fibrillin microfibrils in the three fibrillin-rich lens capsule zones of subjects with the Marfan syndrome., Methods: Capsules were dissected from nine lenses extracted intracapsularly from Marfan syndrome patients. The capsules were divided and mounted flat on gelatin-coated glass slides. ABC immunoperoxidase staining with monoclonal anti-fibrillin antibody was used to visualize and localize fibrillin in these specimens. The staining patterns and microscopic structure of microfibrils were compared to those of normal controls., Results: There were no bundles of fibrillin fibers in Zone I - a 0.75-mm wide peripheral ring of the anterior capsule that normally contains radial bunches of fibrillin fibers; instead, fine disorganized fibrillin-positive fragments were dispersed in this region. The size and shape of the fragments varied among patients. In contrast to normal lenses, there was only light staining for fibrillin in Zone II - a 1-mm wide meshwork of normally fibrillin-rich fibers that encircles the equator and serves as an insertion platform for most zonular fibers. The radial periodic bands of Zone III - a 0.1-mm wide ring on the most peripheral part of the normal posterior capsule - were identifiable in some samples, but stained only faintly for fibrillin., Conclusion: Fibrillin microfibrils are disrupted and fragmented in the lens capsule of patients with the Marfan syndrome. The qualitative, quantitative, and structural abnormalities of fibrillin deposition in the lens capsule of these patients support a causal relationship to lens abnormalities in this disease.
- Published
- 2000
31. A novel locus for Leber congenital amaurosis maps to chromosome 6q.
- Author
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Dharmaraj S, Li Y, Robitaille JM, Silva E, Zhu D, Mitchell TN, Maltby LP, Baffoe-Bonnie AB, and Maumenee IH
- Subjects
- Chromosome Mapping, Consanguinity, Genetic Markers, Genotype, Glycoproteins genetics, Humans, Lod Score, Pedigree, Receptors, GABA genetics, Receptors, GABA-A, Chromosomes, Human, Pair 6 genetics, Extracellular Matrix Proteins, Eye Proteins, Optic Atrophies, Hereditary genetics, Proteoglycans, Receptors, GABA-B
- Published
- 2000
- Full Text
- View/download PDF
32. Retinal detachment in Marfan syndrome.
- Author
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Loewenstein A, Barequet IS, De Juan E Jr, and Maumenee IH
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cryosurgery, Female, Humans, Male, Marfan Syndrome pathology, Middle Aged, Prognosis, Retina pathology, Retinal Detachment pathology, Retinal Detachment surgery, Retrospective Studies, Scleral Buckling, Visual Acuity, Vitrectomy, Marfan Syndrome complications, Retinal Detachment etiology
- Abstract
Purpose: To report postsurgical findings in patients with Marfan syndrome and retinal detachment (RD)., Methods: The authors identified and retrospectively reviewed the charts of one cohort of 12 patients (15 eyes) with Marfan syndrome and RD who were operated on at the Wilmer Institute and a second cohort of 16 such patients (24 eyes) who were operated several years earlier and elsewhere., Results: First cohort--Final visual acuity (VA) was 20/80 or better and the retina was flat in all five phakic eyes (100%). The RD occurred after the eye had undergone lens removal in 10 eyes, 6 of which (60%) had a final VA of 20/80 or better, and 9 of which (90%) had a final VA of 5/200 or better (P = 0.20). Second cohort--The final VA was 20/80 or better and the retina was flat in 6 of the 7 phakic eyes (86%). Among 17 aphakic or pseudophakic eyes, only 5 (29%) had a flat retina and VA of 20/80 or better, whereas 12 (71%) had no light perception (P = 0.03)., Conclusions: The results of RD operations done in the past in Marfan patients were worse when the eye was aphakic. In most cases operated more recently, the prognosis for successful RD repair was good regardless of whether the eye was phakic.
- Published
- 2000
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33. Ehlers-Danlos syndrome.
- Author
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Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, and Geraghty MT
- Subjects
- Humans, Range of Motion, Articular, Ehlers-Danlos Syndrome diagnosis
- Published
- 1999
- Full Text
- View/download PDF
34. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.
- Author
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Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, and Geraghty MT
- Subjects
- Adolescent, Adult, Blood Pressure, Child, Ehlers-Danlos Syndrome diagnosis, Fatigue Syndrome, Chronic diagnosis, Female, Heart Rate, Humans, Hypotension, Orthostatic diagnosis, Male, Ehlers-Danlos Syndrome complications, Fatigue Syndrome, Chronic complications, Hypotension, Orthostatic complications
- Abstract
Objective: To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance., Study Design: Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist., Results: Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS., Conclusions: Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.
- Published
- 1999
- Full Text
- View/download PDF
35. Hereditary macular diseases.
- Author
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Kelly J and Maumenee IH
- Subjects
- Chromosome Aberrations, DNA analysis, Diagnosis, Differential, Eye Diseases, Hereditary diagnosis, Eye Proteins genetics, Humans, Karyotyping, Mutation, Phenotype, Retinal Diseases congenital, Retinal Diseases diagnosis, Eye Diseases, Hereditary genetics, Macula Lutea pathology, Retinal Diseases genetics
- Published
- 1999
- Full Text
- View/download PDF
36. Ocular anterior chamber dysgenesis in craniosynostosis syndromes with a fibroblast growth factor receptor 2 mutation.
- Author
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Okajima K, Robinson LK, Hart MA, Abuelo DN, Cowan LS, Hasegawa T, Maumenee IH, and Jabs EW
- Subjects
- Acrocephalosyndactylia genetics, Craniosynostoses diagnostic imaging, Diagnosis, Differential, Humans, Infant, Limb Deformities, Congenital diagnostic imaging, Male, Phenotype, Radiography, Receptor Protein-Tyrosine Kinases metabolism, Receptor, Fibroblast Growth Factor, Type 2, Receptors, Fibroblast Growth Factor metabolism, Skull diagnostic imaging, Syndrome, Anterior Chamber abnormalities, Craniosynostoses genetics, Mutation, Receptor Protein-Tyrosine Kinases genetics, Receptors, Fibroblast Growth Factor genetics
- Abstract
Fibroblast growth factor receptor (FGFR) mutations have been found in craniosynostosis syndromes with and without limb and/or dermatologic anomalies. Ocular manifestations of FGFR2 syndromes are reported to include shallow orbits, proptosis, strabismus, and hypertelorism, but no ocular anterior chamber, structural abnormalities have been reported until now. We evaluated three unrelated patients with severe Crouzon or Pfeiffer syndrome. Two of them had ocular findings consistent with Peters anomaly, and the third patient had opaque corneae, thickened irides and ciliary bodies, and shallow anterior chambers with occluded angles. Craniosynostosis with and without cloverleaf skull deformity, large anterior fontanelle, hydrocephalus, proptosis, depressed nasal bridge, choanal stenosis/ atresia, midface hypoplasia, and elbow contractures were also present. These patients had airway compromise, seizures, and two died by age 15 months. All three cases were found to have the same FGFR2 Ser351Cys (1231C to G) mutation predicted to form an aberrant disulfide bond(s) and affect ligand binding. Seven patients with isolated Peters anomaly, two patients with Peters plus syndrome, and three cases with typical Antley-Bixler syndrome were screened for this mutation, but none was found. These phenotype/genotype data demonstrate that FGFR2 is involved in the development of the anterior chamber of the eye and that the Ser351Cys mutation is associated with a severe phenotype and clinical course.
- Published
- 1999
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- View/download PDF
37. Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis.
- Author
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Koenekoop R, Pina AL, Loyer M, Davidson J, Robitaille J, Maumenee I, and Tombran-Tink J
- Subjects
- Amino Acid Substitution, Chromosomes, Human, Pair 17, Ethnicity genetics, Eye Proteins genetics, Female, Humans, Male, Mutation, Pedigree, Polymerase Chain Reaction, Polymorphism, Genetic, Polymorphism, Single-Stranded Conformational, Nerve Growth Factors, Optic Atrophies, Hereditary genetics, Proteins genetics, Serpins genetics
- Abstract
Purpose: Leber congenital amaurosis (LCA) has been mapped to chromosome 17p13.1. From the candidate genes mapped to this region, thus far, only Retinal Guanylate Cyclase (RetGC), has been found to have pathogenic LCA mutations, in families from North African origin. However, early reports, demonstrated eight LCA families linked to 17p13.1, but only four of them showed mutations in RetGC. Mapped in proximity to this locus is the candidate gene Pigment Epithelium Derived actor (PEDF), a factor implicated in photoreceptor differentiation and neuronal survival. Our purpose in this study was to identify mutations and polymorphisms in the PEDF gene in LCA patients of diverse ethnic origin., Methods: Automated genotyping with four 17p13.1 markers flanking the PEDF gene was performed to assess homozygosity and PCR-SSCP combined with direct sequencing was used to detect mutations in the PEDF gene in 17 LCA patients., Results: Homozygosity of markers D17S796 and D17S804 was found and four new intragenic basepair alterations were discovered: a Met72Thr polymorphism in exon 3 (T331C), a Thr130Thr polymorphism in exon 4 (T506C), a G to A transition in intron 5 (nine base pairs upstream from splice acceptor site), and a Tyr321Tyr polymorphism in exon 7 (C1079T) were detected., Conclusions: We report the discovery of four new polymorphic alterations in the PEDF gene in LCA patients and exclude by RFLP analysis the PEDF gene as a common cause of Leber congenital amaurosis. These single nucleotide polymorphisms will aid in future linkage analysis of complex multifactorial diseases involving retinal and RPE dysfunctions.
- Published
- 1999
38. Genetic heterogeneity of dominant optic atrophy, Kjer type: Identification of a second locus on chromosome 18q12.2-12.3.
- Author
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Kerrison JB, Arnould VJ, Ferraz Sallum JM, Vagefi MR, Barmada MM, Li Y, Zhu D, and Maumenee IH
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Chromosomes, Human, Pair 3 genetics, Color Perception physiology, DNA analysis, Female, Genetic Linkage genetics, Genetic Markers, Genotype, Humans, Kidd Blood-Group System genetics, Lod Score, Male, Middle Aged, Optic Atrophies, Hereditary pathology, Optic Atrophies, Hereditary physiopathology, Optic Nerve pathology, Pedigree, Visual Acuity physiology, Chromosomes, Human, Pair 18 genetics, Genetic Heterogeneity, Optic Atrophies, Hereditary genetics
- Abstract
Objective: To evaluate a family with autosomal dominant optic atrophy, which has been previously linked to the Kidd blood group., Design: Clinical evaluation with the assessment of visual acuity, color vision, and optic nerve appearance to determine affection status. Linkage analysis using polymorphic DNA markers., Results: Visual acuities ranged from 20/20 to 6/200. Although linkage was excluded for chromosome 3q28-29, markers from chromosome 18 in the vicinity of the Kidd locus were linked to the disorder (D18S34 [maximal lod score (lodmax) of 5.38 at recombination fraction (theta) of 0.14], D18S548 [lod(max)=7.26, theta=0.09], D18S861 [lod(max)= 5.32, theta = 0.07], and D18S479 [lod(max) = 3.28, 0 = 0.12:]). Multipoint linkage analysis demonstrated lod scores of greater than 3 in an approximately 3-centimorgan region flanked by D18S34 and D18S479, using 98% penetrance and a phenocopy rate of 1/50., Conclusions: Dominant optic atrophy is genetically heterogeneous, with loci assigned to chromosomes 3q28-29 and 18q12.2-12.3. Dominant optic atrophy linked to 18q shows intrafamilial variation similar to that previously reported in families linked to 3q, with visual acuities ranging from normal to legal blindness. The overall distribution of visual acuities appears more favorable with the 18q phenotype. Both phenotypes appear to have a similar rate of visual decline.
- Published
- 1999
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- View/download PDF
39. Bestrophin gene mutations in patients with Best vitelliform macular dystrophy.
- Author
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Caldwell GM, Kakuk LE, Griesinger IB, Simpson SA, Nowak NJ, Small KW, Maumenee IH, Rosenfeld PJ, Sieving PA, Shows TB, and Ayyagari R
- Subjects
- Amino Acid Substitution, Bestrophins, Chloride Channels, DNA chemistry, DNA genetics, DNA Mutational Analysis, Family Health, Female, Frameshift Mutation, Humans, Male, Mutation, Mutation, Missense, Pedigree, Point Mutation, Sequence Deletion, Eye Proteins genetics, Macular Degeneration genetics
- Abstract
Best vitelliform macular dystrophy (VMD2) is an autosomal dominant dystrophy with a juvenile age of onset. Mutations in the Bestrophin gene were shown in patients affected with VMD2. In a mutation study, we made three new and interesting observations. First, we identified possible mutation hotspots within the gene, suggesting that particular regions of the protein have greater functional significance than others. Second, we described a 2-bp deletion in a part of the gene where mutations have not previously been reported; this mutation causes a frameshift and subsequent premature termination of the protein. Finally, we have evidence that some mutations are associated with variable expression of the disease, suggesting the involvement of other factors or genes in the disease phenotype., (Copyright 1999 Academic Press.)
- Published
- 1999
- Full Text
- View/download PDF
40. Congenital motor nystagmus linked to Xq26-q27.
- Author
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Kerrison JB, Vagefi MR, Barmada MM, and Maumenee IH
- Subjects
- Female, Haplotypes, Humans, Male, Pedigree, Genetic Linkage, Nystagmus, Pathologic congenital, Nystagmus, Pathologic genetics, X Chromosome
- Abstract
Congenital motor nystagmus (CMN) is a hereditary disorder characterized by bilateral ocular oscillations that begin in the first 6 mo of life. It must be distinguished from those genetic disorders-such as ocular albinism (OA), congenital stationary night blindness (CSNB), and blue-cone monochromatism (BCM)-in which nystagmus accompanies a clinically apparent defect in the visual sensory system. Although CMN is presumed to arise from a neurological abnormality of fixation, it is not known whether the molecular defect is located in the eye or in the brain. It may be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. Three families with CMN inherited in an X-linked, irregularly dominant pattern were investigated with linkage and candidate gene analysis. The penetrance among obligate female carriers was 54%. Evaluation of markers in the region of the genes for X-linked OA, CSNB, and BCM revealed no evidence of linkage, supporting the hypothesis that CMN represents a distinct entity. The gene was mapped to chromosome Xq26-q27 with the following markers: GATA172D05 (LOD score 3.164; recombination fraction [theta] = 0.156), DXS1047 (LOD score 10.296; theta = 0), DXS1192 (LOD score 8.174; theta = 0.027), DXS1232 (LOD score 6.015; theta = 0.036), DXS984 (LOD score 6.695; theta = 0), and GATA31E08 (LOD score 4.940; theta = 0.083). Assessment of haplotypes and multipoint linkage analysis, which gave a maximum LOD score of 10.790 with the 1-LOD-unit support interval spanning approximately 7 cM, place the gene in a region between GATA172D05 and DXS1192. Evaluation of candidate genes CDR1 and SOX3 did not reveal mutations in affected male subjects.
- Published
- 1999
- Full Text
- View/download PDF
41. Demonstration of exclusive cilioretinal vascular system supplying the retina in man: vacant discs.
- Author
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Parsa CF, Cheeseman EW Jr, and Maumenee IH
- Subjects
- Aged, Coloboma diagnosis, Electroretinography, Fluorescein Angiography, Fundus Oculi, Humans, Kidney Diseases diagnosis, Male, Optic Disk pathology, Syndrome, Ultrasonography, Ultrasonography, Doppler, Color, Ciliary Body blood supply, Coloboma physiopathology, Kidney Diseases physiopathology, Optic Disk abnormalities, Optic Disk blood supply, Retinal Vessels physiology
- Abstract
Purpose: To report the fluorescein angiographic and Doppler ultrasonographic findings in a patient with apparent exclusive ciliary vascular supply of the retina of both eyes., Methods: Case report., Results: The ophthalmoscopic appearance of all arterial vessels emanating from both discs was consistent with a cilioretinal origin. Retinal veins also entered each disc peripherally near the margin, leaving the central part of each disc vacant. Fluorescein angiography showed filling of all arterial vessels simultaneous with the early-phase choroidal background flush bilaterally. Color and power Doppler ultrasonographic imaging demonstrated unequivocally the absence of central retinal vessels within the optic nerves. Both discs were normal in size and excavated with central glial tissue present. The clinical history of monocular, alternating episodes of failing vision with partial resolution and the retinal pigmentation patterns bilaterally were consistent with, though not conclusive for, previous episodes of serous retinal detachments. Coincident systemic anomalies consisted of small kidneys with reduced renal parenchyma discovered on ultrasonography, along with chronic interstitial nephritis., Conclusions: The ophthalmoscopic appearance of optic discs with apparent all-cilioretinal vascular supply has been reported previously, but proof of the absence of central retinal vessels requires Doppler ultrasonographic evidence corroborated by angiographic findings, as exemplified in our case report. We describe the association of this disc anomaly with renal parenchymal disease and its distinction from colobomatous defects.
- Published
- 1998
42. Clinical features of autosomal dominant congenital nystagmus linked to chromosome 6p12.
- Author
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Kerrison JB, Koenekoop RK, Arnould VJ, Zee D, and Maumenee IH
- Subjects
- Adult, Aged, Child, Preschool, Electronystagmography, Electroretinography, Eye Movements physiology, Female, Humans, Male, Nerve Fibers physiology, Nystagmus, Pathologic genetics, Nystagmus, Pathologic physiopathology, Ophthalmoscopy, Optic Nerve physiology, Pedigree, Prospective Studies, Retina physiopathology, Visual Acuity physiology, Chromosomes, Human, Pair 6 genetics, Evoked Potentials, Visual, Genetic Linkage, Nystagmus, Pathologic congenital, Nystagmus, Pathologic pathology
- Abstract
Purpose: To describe the clinical features of a large pedigree with autosomal dominant congenital nystagmus linked to chromosome 6p12., Methods: In a prospective evaluation of 54 living family members in a single pedigree, 21 persons were affected with autosomal dominant congenital nystagmus, and clinical examinations were performed on 14. Selected persons underwent further studies, including electroretinography, scanning laser ophthalmoscopy, nerve fiber layer studies, visual evoked potential studies, and eye movement recordings., Results: Among seven affected persons whose parents were able to report whether the nystagmus was present congenitally, onset at birth was noted in two persons and between 3 and 6 months in five persons. Best-corrected binocular Snellen visual acuity ranged from 20/30 to 20/100, with a mode of 20/50. Strabismus was present in 14 examined patients (36%). Eye movement recordings, performed on five persons, included asymmetric pendular (three), asymmetric pendular combined with dual waveform jerk (one), and unidirectional jerk nystagmus (one)., Conclusions: Autosomal dominant congenital nystagmus represents a disorder with variable expressivity. While onset is typically during infancy, it can be noted at birth. Intrafamilial variation in visual acuity, ocular alignment, and nystagmus waveform suggests a role for modifying influences on expression of disease.
- Published
- 1998
- Full Text
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43. Familial Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss: a possible new genetic syndrome.
- Author
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Cunningham ET Jr, Eliott D, Miller NR, Maumenee IH, and Green WR
- Subjects
- Adult, Anterior Eye Segment abnormalities, Anterior Eye Segment pathology, Child, Preschool, Ciliary Body abnormalities, Ciliary Body pathology, Eye Abnormalities pathology, Female, Glaucoma genetics, Glaucoma pathology, Hearing Loss, Sensorineural pathology, Heart Septal Defects, Atrial pathology, Humans, Infant, Male, Middle Aged, Pedigree, Phenotype, Retrospective Studies, Syndrome, Abnormalities, Multiple, Eye Abnormalities genetics, Hearing Loss, Sensorineural genetics, Heart Septal Defects, Atrial genetics
- Abstract
Objective: To describe the clinical and ocular histopathological findings in multiple members of a family with congenital Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss., Methods: We performed a retrospective review of the medical charts and the ocular histopathological material of multiple members of a family., Results: Congenital Axenfeld-Rieger anomaly and glaucoma were inherited by both the proband and her male half-sibling from a phenotypically positive father and 2 different phenotypically negative mothers, suggesting an autosomal dominant inheritance. The proband's male half-sibling and her father also had atrial septal defects and sensorineural hearing loss. The proband's paternal grandmother had severe glaucoma. Histopathological analysis of blind, painful eyes removed from the proband's father and paternal grandmother showed incomplete development of the anterior chamber angle with iris stromal hypoplasia, prominent posterior embryotoxon with iris adhesions, and abnormal position and insertion of the ciliary muscles., Conclusions: This is the first description of coexisting Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss in multiple members of a single family. The iris, trabecular meshwork, and large portions of the cardiac intraventricular septum all arise from neural crest anlagen, thus supporting the notion that anterior segment dysgenesis represents a developmental disorder of the neural crest.
- Published
- 1998
- Full Text
- View/download PDF
44. Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta-crystallin gene CRYBB2.
- Author
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Litt M, Carrero-Valenzuela R, LaMorticella DM, Schultz DW, Mitchell TN, Kramer P, and Maumenee IH
- Subjects
- Amino Acid Sequence, Base Sequence, Cataract congenital, Deoxyribonucleases, Type II Site-Specific genetics, Deoxyribonucleases, Type II Site-Specific metabolism, Exons, Female, Homozygote, Humans, Introns, Male, Molecular Sequence Data, Polymerase Chain Reaction, Cataract genetics, Crystallins genetics, Genes, Dominant, Mutation
- Abstract
Congenital cataracts are a common major abnormality of the eye that frequently cause blindness in infants. At least a third of all cases are familial; autosomal dominant congenital cataract (ADCC) appears to be the most common familial form in the Western world. Cerulean cataracts have peripheral bluish and white opacifications in concentric layers with occasional central lesions arranged radially. Although the opacities may be observed during fetal development and childhood, usually visual acuity is only mildly reduced until adulthood, when lens extraction is generally necessary. We have been studying a family (ADCC-1) with cerulean blue ADCC, in which the affected daughter of a first cousin mating was presumed to be homozygous for the cataract gene. Recently, we mapped an ADCC gene in this family to a region of chromosome 22 containing three beta-crystallin genes. Here we report that a chain-termination mutation in CRYBB2 is associated with ADCC in this family.
- Published
- 1997
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- View/download PDF
45. A second gene for cerulean cataracts maps to the beta crystallin region on chromosome 22.
- Author
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Kramer P, Yount J, Mitchell T, LaMorticella D, Carrero-Valenzuela R, Lovrien E, Maumenee I, and Litt M
- Subjects
- Cataract physiopathology, Chromosome Mapping, Female, Genetic Linkage, Humans, Male, Pedigree, Pseudogenes, Cataract genetics, Chromosomes, Human, Pair 22, Crystallins genetics
- Abstract
Congenital cataracts are one of the most common major eye abnormalities and often lead to blindness in infants. At least a third of all cases are familial. Within this group, highly penetrant, autosomal dominant forms of congenital cataracts (ADCC) are most common. ADCC is a genetically heterogeneous group of disorders, in which at least eight different loci have been identified for nine clinically distinct forms. Among these, Armitage et al. (Nature Genet. 9: 37-40, 1995) mapped a gene for cerulean blue cataracts to chromosome 17q24. Bodker et al. (Am. J. Med. Genet. 37: 54-59, 1990) described a large family with cerulean blue cataracts, in which the affected daughter of affected first cousins was presumed to be homozygous for the purported gene. We report linkage in this family to the region on chromosome 22q that includes two beta crystallin genes (CRYBB2, CRYBB3) and one pseudogene (CRYBB2P1). The affected female in question is homozygous at all markers.
- Published
- 1996
- Full Text
- View/download PDF
46. A gene for autosomal dominant congenital nystagmus localizes to 6p12.
- Author
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Kerrison JB, Arnould VJ, Barmada MM, Koenekoop RK, Schmeckpeper BJ, and Maumenee IH
- Subjects
- Chromosome Mapping, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 7, Female, Genes, Recessive, Genetic Linkage, Genetic Markers, Haplotypes, Humans, Infant, Infant, Newborn, Male, Nystagmus, Pathologic physiopathology, Pedigree, Translocation, Genetic, Chromosomes, Human, Pair 6, Genes, Dominant, Nystagmus, Pathologic genetics, X Chromosome
- Abstract
Congenital nystagmus is an idiopathic disorder characterized by bilateral ocular oscillations usually manifest during infancy. Vision is typically decreased due to slippage of images across the fovea. As such, visual acuity correlates with nystagmus intensity, which is the amplitude and frequency of eye movements at a given position of gaze. X-linked, autosomal dominant, and autosomal recessive pedigrees have been described, but no mapping studies have been published. We recently described a large pedigree with autosomal dominant congenital nystagmus. A genome-wide search resulted in six markers on 6p linked by two-point analysis at theta = 0 (D6S459, D6S452, D6S465, FTHP1, D6S257, D6S430). Haplotype analysis localizes the gene for autosomal dominant congenital motor nystagmus to an 18-cM region between D6S271 and D6S455.
- Published
- 1996
- Full Text
- View/download PDF
47. The Castroviejo square graft.
- Author
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Haselwood DM, Lesko WS, Maumenee IH, Stark WJ, and Green WR
- Subjects
- Aged, Cornea pathology, Cornea surgery, Corneal Dystrophies, Hereditary etiology, Corneal Dystrophies, Hereditary pathology, Corneal Dystrophies, Hereditary surgery, Female, Graft Rejection etiology, Graft Rejection pathology, Graft Rejection surgery, Humans, Keratoplasty, Penetrating pathology, Male, Middle Aged, Reoperation, Cornea ultrastructure, Keratoplasty, Penetrating methods
- Abstract
The histopathologic features of three keratoplasty specimens from three cases involving square graft procedures performed by Dr. Castroviejo are reported. Light and electron microscopy were performed. In two of the cases, repeat keratoplasties were performed because of recurrent corneal dystrophies. In the third case, a repeat keratoplasty was performed because of graft failure.
- Published
- 1996
48. Photoaversion in Leber's congenital amaurosis.
- Author
-
Traboulsi EI and Maumenee IH
- Subjects
- Child, Electroretinography, Humans, Male, Optic Atrophies, Hereditary diagnosis, Optic Atrophies, Hereditary physiopathology, Retinal Cone Photoreceptor Cells pathology, Retinal Cone Photoreceptor Cells physiopathology, Retinal Rod Photoreceptor Cells pathology, Retinal Rod Photoreceptor Cells physiopathology, Vision Disorders diagnosis, Vision Disorders physiopathology, Blindness congenital, Light, Optic Atrophies, Hereditary complications, Vision Disorders complications
- Abstract
Photoaversion is a prominent symptom of a number of infantile genetic ocular disorder such as congenital glaucoma, aniridia, albinism, and cone dystrophies including achromatopsia. Photoaversion has not been widely recognized as a clinical feature of Leber's congenital amaurosis. We present two patients who were diagnosed clinically with achromatopsia because of nystagmus, absent color vision, reduced visual acuity, and moderately severe photoaversion in the absence of anterior segment abnormalities. The photopic and scotopic responses of the electroretinogram (E R G) were nonrecordable in both patients indicating involvement of both cone and rod systems. The diagnosis was then revised to one of Leber's congenital amaurosis. Photoaversion can be a prominent clinical feature in some patients with Leber's congenital amaurosis. The E R G clinches the diagnosis. These patients may constitute a distinct genetic subtype of the disease and molecular genetic studies will help resolve this issue.
- Published
- 1995
- Full Text
- View/download PDF
49. Immunohistochemical localization of fibrillin in human ocular tissues. Relevance to the Marfan syndrome.
- Author
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Wheatley HM, Traboulsi EI, Flowers BE, Maumenee IH, Azar D, Pyeritz RE, and Whittum-Hudson JA
- Subjects
- Aged, Aged, 80 and over, Anterior Eye Segment chemistry, Bruch Membrane chemistry, Choroid chemistry, Extracellular Matrix Proteins analysis, Fibrillins, Humans, Immunoenzyme Techniques, Middle Aged, Sclera chemistry, Eye chemistry, Marfan Syndrome pathology, Microfilament Proteins analysis
- Abstract
Objective: To better understand the ocular manifestations of the Marfan syndrome, we investigated the distribution of fibrillin in normal human ocular tissues. Fibrillin, a microfibrillar glycoprotein component of the extracellular matrix, has been found to be the defective gene product in the Marfan syndrome., Methods: Frozen sections from seven pairs of normal eyes were stained with mouse anti-human fibrillin antibodies using the avidin-biotin immunoperoxidase technique., Results: In the anterior segment, the following exhibited positive staining for fibrillin: the lens capsule and zonules; connective tissues of the iris, ciliary body, ciliary processes, and conjunctiva; and the basement membrane regions of the corneal epithelium and endothelium of Schlemm's canal. Posteriorly, fibrillin localized to the lamina cribrosa, sclera, choroid, and Bruch's membrane., Conclusions: Fibrillin is widely distributed in ocular connective tissues. The implications of defects in these tissues and the resultant ocular abnormalities in the Marfan syndrome such as ectopia lentis and glaucoma are discussed.
- Published
- 1995
- Full Text
- View/download PDF
50. Effects of strabismus surgery on refraction in children.
- Author
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Denis D, Bardot J, Volot F, Saracco JB, and Maumenee IH
- Subjects
- Astigmatism physiopathology, Child, Child, Preschool, Esotropia physiopathology, Female, Humans, Male, Oculomotor Muscles physiopathology, Prospective Studies, Refraction, Ocular, Astigmatism etiology, Esotropia surgery, Oculomotor Muscles surgery, Postoperative Complications
- Abstract
We assessed 115 eyes of 59 children with esotropia 2-3 months postoperatively to evaluate the effects of strabismus surgery on refraction. Three variables were measured: spherical equivalent, and cylinder power and axis. The mean changes in spherical equivalent were non-significant. The axis of postoperative astigmatism moved towards 'with-the-rule', thus improving refraction. The amount of recession and the consequent changes in cylinder power were inversely related. The results showed a significant change in cylinder axis after recession of the inferior oblique. Recession-tucking procedures led to the largest changes in cylinder power.
- Published
- 1995
- Full Text
- View/download PDF
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