27 results on '"Genetic Diseases, X-Linked physiopathology"'
Search Results
2. Differential adaptations in rod outer segment disc membranes in different models of congenital stationary night blindness.
- Author
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Senapati S and Park PS
- Subjects
- Animals, Disease Models, Animal, Mice, Mice, Transgenic, Signal Transduction, Vision, Ocular, Adaptation, Physiological, Eye Diseases, Hereditary physiopathology, Genetic Diseases, X-Linked physiopathology, Myopia physiopathology, Night Blindness physiopathology, Rod Cell Outer Segment physiology
- Abstract
Rod photoreceptor cells initiate scotopic vision when the light receptor rhodopsin absorbs a photon of light to initiate phototransduction. These photoreceptor cells are exquisitely sensitive and have adaptive mechanisms in place to maintain optimal function and to overcome dysfunctional states. One adaptation rod photoreceptor cells exhibit is in the packing properties of rhodopsin within the membrane. The mechanism underlying these adaptations is unclear. Mouse models of congenital stationary night blindness with different molecular causes were investigated to determine which signals are important for adaptations in rod photoreceptor cells. Night blindness in these mice is caused by dysfunction in either rod photoreceptor cell signaling or bipolar cell signaling. Changes in the packing of rhodopsin within photoreceptor cell membranes were examined by atomic force microscopy. Mice expressing constitutively active rhodopsin did not exhibit any adaptations, even under constant dark conditions. Mice with disrupted bipolar cell signaling exhibited adaptations, however, they were distinct from those in mice with disrupted phototransduction. These differential adaptations demonstrate that although multiple molecular defects can lead to a similar primary defect causing disease (i.e., night blindness), they can cause different secondary effects (i.e., adaptations). The lighting environment or signaling defects present from birth and during early rearing can condition mice and affect the adaptations occurring in more mature animals. A comparison of effects in wild-type mice, mice with defective phototransduction, and mice with defective bipolar cell signaling, indicated that bipolar cell signaling plays a role in this conditioning but is not required for adaptations in more mature animals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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3. Can Structural Grading of Foveal Hypoplasia Predict Future Vision in Infantile Nystagmus?: A Longitudinal Study.
- Author
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Rufai SR, Thomas MG, Purohit R, Bunce C, Lee H, Proudlock FA, and Gottlob I
- Subjects
- Albinism, Oculocutaneous diagnosis, Albinism, Oculocutaneous physiopathology, Child, Preschool, Color Vision Defects diagnosis, Color Vision Defects physiopathology, Eye Abnormalities classification, Female, Follow-Up Studies, Fovea Centralis diagnostic imaging, Genetic Diseases, X-Linked physiopathology, Humans, Infant, Longitudinal Studies, Male, Nystagmus, Congenital physiopathology, Prospective Studies, Tomography, Optical Coherence, Vision Disorders physiopathology, Visual Acuity physiology, Eye Abnormalities pathology, Fovea Centralis abnormalities, Genetic Diseases, X-Linked diagnosis, Nystagmus, Congenital diagnosis, Vision Disorders diagnosis
- Abstract
Purpose: To evaluate structural grading and quantitative segmentation of foveal hypoplasia using handheld OCT, versus preferential looking (PL), as predictors of future vision in preverbal children with infantile nystagmus., Design: Longitudinal cohort study., Participants: Forty-two patients with infantile nystagmus (19 with albinism, 17 with idiopathic infantile nystagmus, and 6 with achromatopsia) were examined., Methods: Spectral-domain handheld OCT was performed in preverbal children up to 36 months of age. Foveal tomograms were graded using our 6-point grading system for foveal hypoplasia and were segmented for quantitative analysis: photoreceptor length, outer segment (OS) length, and foveal developmental index (FDI; a ratio of inner layers versus total foveal thickness). Patients were followed up until they could perform chart visual acuity (VA) testing. Data were analyzed using linear mixed regression models. Visual acuity predicted by foveal grading was compared with prediction by PL, the current gold standard for visual assessment in infants and young children., Main Outcome Measures: Grade of foveal hypoplasia, quantitative parameters (photoreceptor length, OS length, FDI), and PL VA were obtained in preverbal children for comparison with future chart VA outcomes., Results: We imaged 81 eyes from 42 patients with infantile nystagmus of mean age 19.8 months (range, 0.9-33.4 months; standard deviation [SD], 9.4 months) at the first handheld OCT scan. Mean follow-up was 44.1 months (range, 18.4-63.2 months; SD, 12.0 months). Structural grading was the strongest predictor of future VA (grading: r = 0.80, F = 67.49, P < 0.0001) compared with quantitative measures (FDI: r = 0.74, F = 28.81, P < 0.001; OS length: r = 0.65; F = 7.94, P < 0.008; photoreceptor length: r = 0.65; F = 7.94, P < 0.008). Preferential looking was inferior to VA prediction by foveal grading (PL: r = 0.42, F = 3.12, P < 0.03)., Conclusions: Handheld OCT can predict future VA in infantile nystagmus. Structural grading is a better predictor of future VA than quantitative segmentation and PL testing. Predicting future vision may avert parental anxiety and may optimize childhood development., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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4. Generation of an induced pluripotent stem cell line (FRIMOi007-A) derived from an incomplete achromatopsia patient carrying a novel homozygous mutation in PDE6C gene.
- Author
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Domingo-Prim J, Abad-Morales V, Riera M, Navarro R, Corcostegui B, and Pomares E
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- Adult, Cell Differentiation, Cell Line metabolism, Cells, Cultured, Color Vision Defects metabolism, Color Vision Defects physiopathology, Cyclic Nucleotide Phosphodiesterases, Type 6 metabolism, Eye Proteins metabolism, Fibroblasts cytology, Fibroblasts metabolism, Genetic Diseases, X-Linked metabolism, Genetic Diseases, X-Linked physiopathology, Homozygote, Humans, Induced Pluripotent Stem Cells cytology, Male, Mutation, Cell Line cytology, Color Vision Defects genetics, Cyclic Nucleotide Phosphodiesterases, Type 6 genetics, Eye Proteins genetics, Genetic Diseases, X-Linked genetics, Induced Pluripotent Stem Cells metabolism
- Abstract
Incomplete achromatopsia (ACHM) is a disorder in which there is function defect of cone photoreceptors in the retina and individuals with such disease retain residual color vision. Here, we have generated an induced pluripotent stem cell (iPSC) line carrying a homozygous mutation in the PDE6C gene, already related with this vision disorder. Skin fibroblasts from a patient with incomplete ACHM were reprogrammed to iPSCs by the non-integrative Sendai-virus method. Finally, the iPSC line has been characterized expressing the pluripotency markers and being capable to differentiate to endoderm, mesoderm and ectoderm in vitro., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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5. A novel PIGA variant associated with severe X-linked epilepsy and profound developmental delay.
- Author
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Low KJ, James M, Sharples PM, Eaton M, Jenkinson S, Study DDD, and Smithson SF
- Subjects
- Adolescent, Developmental Disabilities physiopathology, Developmental Disabilities therapy, Epilepsy physiopathology, Epilepsy therapy, Genetic Diseases, X-Linked physiopathology, Genetic Diseases, X-Linked therapy, Humans, Male, Severity of Illness Index, Developmental Disabilities genetics, Epilepsy genetics, Genetic Diseases, X-Linked genetics, Genetic Variation, Membrane Proteins genetics
- Published
- 2018
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6. Slowly progressive leukodystrophy in an adolescent male with phosphoglycerate kinase deficiency.
- Author
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Baba S, Kobayashi A, Yokoyama H, Moriyama K, Kashimada A, Oyama J, Owada A, Oyama S, Morio T, and Takagi M
- Subjects
- Adolescent, Brain diagnostic imaging, Diagnosis, Differential, Diet, Ketogenic adverse effects, Disease Progression, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked therapy, Humans, Male, Metabolism, Inborn Errors genetics, Metabolism, Inborn Errors therapy, Phosphoglycerate Kinase genetics, Genetic Diseases, X-Linked complications, Genetic Diseases, X-Linked physiopathology, Leukoencephalopathies complications, Leukoencephalopathies physiopathology, Metabolism, Inborn Errors complications, Metabolism, Inborn Errors physiopathology, Phosphoglycerate Kinase deficiency
- Abstract
We report the case of an 18-year-old man with a phosphoglycerate kinase (PGK) deficiency who had slowly progressive leukodystrophy during adolescence. The patient had a history of severe neonatal jaundice, hemolytic crisis with rhabdomyolysis triggered by febrile viral infections, dysarthria, and intellectual disability during early childhood. Clumsiness in walking and writing became obvious at ∼10years of age. Evaluations performed by us on the 18-year-old patient confirmed the presence of pyramidal tract signs, increased muscle tone, and generalized dystonia. Brain magnetic resonance (MR) imaging revealed leukodystrophy in the periventricular white matter, posterior limbs of the internal capsule, dorsal pons, and middle cerebellar peduncles. Compared to MR images acquired at 9years of age, MR images acquired at 18years of age showed that the white matter atrophy had progressed. The PGK deficiency was diagnosed by identifying a known missense mutation in PGK1 (c.1060G>C) through comprehensive target capture sequencing and by observing low PGK activity in his red blood cells. The patient underwent a ketogenic diet for 2weeks, which we expected would increase adenosine triphosphate levels through sources other than the PGK-associated glycolytic pathway. The diet was not tolerated owing to the unexpected emergence of hemolysis. Hemolytic anemia, neurological dysfunction, and myopathy are often associated with PGK deficiencies. However, leukodystrophy as a symptom of PGK deficiency has not been reported previously. Our case highlights the progressive nature of the neurological complications related to PGK deficiencies. Therefore, long-term follow-up is recommended, even if neurological impairments are not obvious during childhood., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
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7. Arts syndrome with a novel missense mutation in the PRPS1 gene: A case report.
- Author
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Maruyama K, Ogaya S, Kurahashi N, Umemura A, Yamada K, Hashiguchi A, Takashima H, Torres RJ, and Aso K
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- Ataxia diagnostic imaging, Ataxia physiopathology, Ataxia therapy, Brain diagnostic imaging, Deaf-Blind Disorders diagnostic imaging, Deaf-Blind Disorders physiopathology, Deaf-Blind Disorders therapy, Family, Genetic Diseases, X-Linked diagnostic imaging, Genetic Diseases, X-Linked physiopathology, Genetic Diseases, X-Linked therapy, Humans, Infant, Male, Neural Conduction genetics, Pedigree, Ataxia genetics, Deaf-Blind Disorders genetics, Genetic Diseases, X-Linked genetics, Mutation, Missense, Ribose-Phosphate Pyrophosphokinase genetics
- Abstract
Arts syndrome is characterized by early-onset hypotonia, ataxia, intellectual disability, sensorineural hearing impairment, progressive optic atrophy, and a tendency to develop infections. Arts syndrome is an X-linked disorder caused by a loss-of-function mutation in the PRPS1 gene, which encodes phosphoribosylpyrophosphate synthetase 1. Only three families have been reported. Here, we report another family with Arts syndrome. The initial symptoms of the 1-year-old proband were hypotonia and ataxia, worsening recurrent infection-triggered muscle weakness, motor and intellectual developmental delay, and hearing loss. Both central nervous system involvement and peripheral neuropathy were demonstrated. His three maternal uncles had died before the age of 3years. A genetic analysis of PRPS1 revealed a novel missense mutation, c.367C>G (p.His123Asp). PRPS enzymatic activity was markedly reduced in the patient. His mother was supposed to be an asymptomatic carrier. Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
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8. Expanding phenotype of p.Ala140Val mutation in MECP2 in a 4 generation family with X-linked intellectual disability and spasticity.
- Author
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Lambert S, Maystadt I, Boulanger S, Vrielynck P, Destrée A, Lederer D, and Moortgat S
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- Adult, Aged, Ataxia complications, Ataxia physiopathology, Epilepsy complications, Epilepsy physiopathology, Female, Genes, X-Linked genetics, Genetic Diseases, X-Linked complications, Genetic Diseases, X-Linked physiopathology, Humans, Intellectual Disability complications, Intellectual Disability physiopathology, Male, Mental Retardation, X-Linked complications, Mental Retardation, X-Linked physiopathology, Microcephaly complications, Microcephaly physiopathology, Middle Aged, Muscle Spasticity complications, Muscle Spasticity genetics, Muscle Spasticity physiopathology, Ocular Motility Disorders complications, Ocular Motility Disorders physiopathology, Pedigree, Phenotype, Rett Syndrome complications, Rett Syndrome physiopathology, Ataxia genetics, Epilepsy genetics, Genetic Diseases, X-Linked genetics, Intellectual Disability genetics, Mental Retardation, X-Linked genetics, Methyl-CpG-Binding Protein 2 genetics, Microcephaly genetics, Ocular Motility Disorders genetics, Rett Syndrome genetics
- Abstract
Mutations in MECP2 (MIM #312750), located on Xq28 and encoding a methyl CpG binding protein, are classically associated with Rett syndrome in female patients, with a lethal effect in hemizygous males. However, MECP2 mutations have already been reported in surviving males with severe neonatal-onset encephalopathy, or with X-linked intellectual disability associated with psychosis, pyramidal signs, parkinsonian features and macro-orchidism (PPM-X syndrome; MIM3 #300055). Here we report on the identification of the p.Ala140Val mutation in the MECP2 gene in 4 males and 3 females of a large Caucasian family affected with X-linked intellectual disability. Females present with mild cognitive impairment and speech difficulties. Males have moderate intellectual disability, impaired language development, friendly behavior, slowly progressive spastic paraparesis and dystonic movements of the hands. Two of them show microcephaly. The p.Ala140Val mutation is recurrent, as it was already described in 4 families with X-linked mental retardation and in three sporadic male patients with intellectual disability. We further delineate the phenotype associated with the p.Ala140Val mutation, illustrating a variable expressivity even within a given family, and we compare our patients with previous reported cases in the literature., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
- Published
- 2016
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9. Chromosome Xq28 duplication encompassing MECP2: Clinical and molecular analysis of 16 new patients from 10 families in China.
- Author
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Yi Z, Pan H, Li L, Wu H, Wang S, Ma Y, and Qi Y
- Subjects
- Adolescent, Adult, Child, Child, Preschool, China, Comparative Genomic Hybridization methods, Craniofacial Abnormalities physiopathology, Developmental Disabilities physiopathology, Facies, Female, Genes, Duplicate, Genetic Diseases, X-Linked physiopathology, Humans, Infant, Intellectual Disability physiopathology, Male, Pedigree, Phenotype, Sex Chromosome Disorders physiopathology, X Chromosome Inactivation genetics, Chromosome Duplication genetics, Craniofacial Abnormalities genetics, Developmental Disabilities genetics, Genetic Diseases, X-Linked genetics, Intellectual Disability genetics, Methyl-CpG-Binding Protein 2 genetics, Segmental Duplications, Genomic, Sex Chromosome Disorders genetics
- Abstract
Introduction: Chromosome Xq28 duplications encompassing methyl-CpG-binding protein 2 gene (MECP2) are observed most in males with a severe neurodevelopmental disorder associated with hypotonia, spasticity, severe learning disability, delayed psychomotor development, and recurrent pulmonary infections. Most female carriers are asymptomatic due to extremely or completely skewed X-inactivation., Methods: A retrospective clinical and molecular study was conducted to examine 16 patients and two fetuses from 10 families who were identified among patients with Xq28 duplications who presented at genetic clinics., Results: Of all 16 patients, 10 had a family history. Only one patient was female. All of the patients had no relevant pre-natal history. All of the patients exhibited severe psychomotor developmental delay, infantile hypotonia and recurrent infections. Some of the patients exhibited cardiac abnormalities, gastrointestinal mobility problems, hydrocele of tunica vaginalis, cryptorchidism, and autistic phenotypes. Additionally, neonatal kidney calculus, premature closure of the fontanel and pulmonary sequestration were found in the patients. Duplication sizes in these patients range from 0.21 to 14.391 Mb (most were smaller than 1 Mb), and all the duplications included host cell factor C1 (HCFC1), interleukin-1 receptor-associated kinase 1 (IRAK1), and MECP2. Bioinformatics analysis revealed that approximately half of the distal breakpoints were located within the low-copy repeats (LCRs), which may be involved in the recombination. The two fetuses were found to be healthy in the prenatal diagnosis., Conclusion: This is the first large cohort of patients with MECP2 duplication syndrome, including a female, reported in China. Interestingly, neonatal kidney calculus, premature closure of the fontanel and pulmonary sequestration were first reported in this syndrome. However, it was difficult to distinguish if these patients represented unique cases or if these phenotypes can be considered as part of the syndrome. The correlation between the infrequent phenotypes and duplications/genes in the duplication region needs further systematic delineation. In conclusion, our study suggested that it is important to emphasize molecular genetic analysis in patients with developmental delay/intellectual disability and recurrent infections and that it is especially important for familial female carriers to accept prenatal diagnosis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
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- 2016
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10. Visual Function in Carriers of X-Linked Retinitis Pigmentosa.
- Author
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Comander J, Weigel-DiFranco C, Sandberg MA, and Berson EL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Dark Adaptation, Electroretinography, Eye Proteins genetics, Female, GTP-Binding Proteins, Genetic Association Studies, Genotyping Techniques, Humans, Infant, Intracellular Signaling Peptides and Proteins genetics, Membrane Proteins genetics, Middle Aged, Photic Stimulation, Retina physiopathology, Retrospective Studies, Genetic Diseases, X-Linked physiopathology, Heterozygote, Retinitis Pigmentosa genetics, Retinitis Pigmentosa physiopathology, Vision Disorders physiopathology, Visual Acuity physiology, Visual Fields physiology
- Abstract
Purpose: To determine the frequency and severity of visual function loss in female carriers of X-linked retinitis pigmentosa (XLRP)., Design: Case series., Participants: Two hundred seventy-six XLRP carriers with cross-sectional data (n = 242) and longitudinal data (n = 34; median follow-up, 16 years; follow-up range, 3-37 years). Half of the carriers were from RPGR- or RP2-genotyped families., Methods: Retrospective medical records review., Main Outcome Measures: Visual acuities, visual field areas, final dark adaptation thresholds, and full-field electroretinography (ERG) responses to 0.5-Hz and 30-Hz flashes., Results: In genotyped families, 40% of carriers showed a baseline abnormality on at least 1 of 3 psychophysical tests. There was a wide range of function among carriers. For example, 3 of 121 (2%) genotyped carriers were legally blind because of poor visual acuity, some as young as 35 years. Visual fields were less affected than visual acuity. In all carriers, the average ERG amplitude to 30-Hz flashes was approximately 50% of normal, and the average exponential rate of amplitude loss over time was half that of XLRP males (3.7%/year vs. 7.4%/year, respectively). Among obligate carriers with affected fathers, sons, or both, 53 of 55 (96%) had abnormal baseline ERG results. Some carriers who initially had completely normal fundi in both eyes went on to experience moderately decreased vision, although not legal blindness. Among carriers with RPGR mutations, those with mutations in ORF15, compared with those in exons 1-14, had worse final dark adaptation thresholds and lower 0.5-Hz and 30-Hz ERG amplitudes., Conclusions: Most carriers of XLRP had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. Carriers of RPGR ORF15 mutations tended to have worse visual function than carriers of RPGR exon 1 through 14 mutations. Because XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected men, these observations were consistent with the Lyon hypothesis of random X-inactivation., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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11. Correlation of retinal structure and function in choroideremia carriers.
- Author
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Edwards TL, Groppe M, Jolly JK, Downes SM, and MacLaren RE
- Subjects
- Adolescent, Adult, Aged, Ampholyte Mixtures, Choroideremia genetics, CpG Islands genetics, Female, Genetic Diseases, X-Linked genetics, Heterozygote, Humans, Male, Middle Aged, Phenotype, Sensory Thresholds, Visual Acuity physiology, Visual Field Tests, Visual Fields physiology, Young Adult, Choroideremia physiopathology, Genetic Diseases, X-Linked physiopathology, Retina physiopathology
- Published
- 2015
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12. Rates of decline in regions of the visual field defined by frequency-domain optical coherence tomography in patients with RPGR-mediated X-linked retinitis pigmentosa.
- Author
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Birch DG, Locke KG, Felius J, Klein M, Wheaton DK, Hoffman DR, and Hood DC
- Subjects
- Adolescent, Adult, Child, Female, Follow-Up Studies, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked genetics, Humans, Male, Prospective Studies, Retinitis Pigmentosa diagnosis, Retinitis Pigmentosa genetics, Sensitivity and Specificity, Tomography, Optical Coherence, Visual Acuity physiology, Visual Field Tests, Young Adult, Eye Proteins genetics, Genetic Diseases, X-Linked physiopathology, Mutation, Retina physiopathology, Retinitis Pigmentosa physiopathology, Vision Disorders physiopathology, Visual Fields physiology
- Abstract
Purpose: To determine whether annual decline in visual field sensitivity is greater in the transition zone at the edge of the frequency-domain optical coherence tomography (fdOCT) inner segment ellipsoid zone (EZ) than at other locations in the visual field., Design: Prospective, longitudinal, observational study., Participants: Forty-four patients with X-linked retinitis pigmentosa (XLRP) resulting from a mutation in the RPGR gene., Methods: Static perimetric fields (Humphrey 30-2; Carl Zeiss Meditec, Dublin, CA) were obtained annually for 4 years. Beginning with year 2, fdOCT scans were obtained annually with a Heidelberg Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany)., Main Outcome Measures: The rate of visual field decline at locations near the edge of the EZ compared with the rates for the macula and in the mid periphery., Results: Sensitivity just inside and outside the edge of the EZ declined at rates of 0.84 and 0.92 dB/year, respectively. By comparison, average sensitivity in the macula and mid periphery declined by 0.38 and 0.61 dB/year, respectively., Conclusions: The edge of the EZ in each patient with XLRP indicates a transition zone between relatively healthy and relatively degenerate retina. The annual loss of sensitivity in the transition zone is more rapid than it is elsewhere in the retina., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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13. Evolving practice: X-linked agammaglobulinemia and lung transplantation.
- Author
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Barnes S, Kotecha S, Douglass JA, Paul E, Hore-Lacy F, Stirling R, Snell GI, and Westall GP
- Subjects
- Adult, Humans, Male, Middle Aged, Agammaglobulinemia physiopathology, Genetic Diseases, X-Linked physiopathology, Lung Transplantation
- Abstract
X-linked agammaglobulinemia (XLA) is a rare primary humoral immunodeficiency syndrome characterized by agammaglobulinemia, recurrent infections and bronchiectasis. Despite the association with end-stage bronchiectasis, the literature on XLA and lung transplantation is extremely limited. We report a series of 6 XLA patients with bronchiectasis who underwent lung transplantation. Short-term outcomes were excellent however long-term outcomes were disappointing with a high incidence of pulmonary sepsis and chronic lung allograft dysfunction (CLAD)., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2015
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14. Genotype and phenotype of 101 dutch patients with congenital stationary night blindness.
- Author
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Bijveld MM, Florijn RJ, Bergen AA, van den Born LI, Kamermans M, Prick L, Riemslag FC, van Schooneveld MJ, Kappers AM, and van Genderen MM
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Electroretinography, Eye Diseases, Hereditary physiopathology, Female, Genetic Diseases, X-Linked physiopathology, Genotype, Humans, Infant, Male, Middle Aged, Mutation, Myopia physiopathology, Netherlands, Night Blindness physiopathology, Phenotype, Refractive Errors, Sensory Thresholds physiology, Visual Acuity physiology, Young Adult, Eye Diseases, Hereditary genetics, Eye Proteins genetics, Genetic Diseases, X-Linked genetics, Myopia genetics, Night Blindness genetics
- Abstract
Objective: To investigate the relative frequency of the genetic causes of the Schubert-Bornschein type of congenital stationary night blindness (CSNB) and to determine the genotype-phenotype correlations in CSNB1 and CSNB2., Design: Clinic-based, longitudinal, multicenter study., Participants: A total of 39 patients with CSNB1 from 29 families and 62 patients with CSNB2 from 43 families., Methods: Patients underwent full ophthalmologic and electrophysiologic examinations. On the basis of standard electroretinograms (ERGs), patients were diagnosed with CSNB1 or CSNB2. Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in NYX, TRPM1, GRM6, and GPR179 in patients with CSNB1 and CACNA1F and CABP4 in patients with CSNB2., Main Outcome Measures: Data included genetic cause of CSNB, refractive error, visual acuity, nystagmus, strabismus, night blindness, photophobia, color vision, dark adaptation (DA) curve, and standard ERGs., Results: A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a "square-wave" appearance in CSNB1 and a decreased b-wave in CSNB2. Mutations causing CSNB1 were found in NYX (20 patients, 13 families), TRPM1 (10 patients, 9 families), GRM6 (4 patients, 3 families), and GPR179 (2 patients, 1 family). Congenital stationary night blindness 2 was primarily caused by mutations in CACNA1F (55 patients, 37 families). Only 3 patients had causative mutations in CABP4 (2 families). Patients with CSNB1 mainly had rod-related problems, and patients with CSNB2 had rod- and cone-related problems. The visual acuity on average was better in CSNB1 (0.30 logarithm of the minimum angle of resolution [logMAR]) than in CSNB2 (0.52 logMAR). All patients with CSNB1 and only 54% of the patients with CSNB2 reported night blindness. The dark-adapted threshold was on average more elevated in CSNB1 (3.0 log) than in CSNB2 (1.8 log). The 3 patients with CABP4 had a relative low visual acuity, were hyperopic, had severe nonspecific color vision defects, and had only 1.0 log elevated DA threshold., Conclusions: Congenital stationary night blindness 1, despite different causative mutations, shows 1 unique CSNB1 phenotype. Congenital stationary night blindness 2 caused by mutations in CABP4 merely shows cone-related problems and therefore appears to be distinct from CSNB2 caused by mutations in CACNA1F., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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15. Resting beta hypersynchrony in secondary dystonia and its suppression during pallidal deep brain stimulation in DYT3+ Lubag dystonia.
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Whitmer D, de Solages C, Hill BC, Yu H, and Bronte-Stewart H
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- Adult, Female, Functional Laterality, Globus Pallidus pathology, Humans, Male, Middle Aged, Spectrum Analysis, Treatment Outcome, Young Adult, Beta Rhythm physiology, Deep Brain Stimulation methods, Dystonic Disorders physiopathology, Dystonic Disorders therapy, Genetic Diseases, X-Linked physiopathology, Genetic Diseases, X-Linked therapy, Globus Pallidus physiology, Rest
- Abstract
Objectives: 1) To characterize patterns of globus pallidus interna neural synchrony in patients with secondary dystonia; 2) to determine whether neural hypersynchrony in the globus pallidus externa (GPe) and interna (GPi) is attenuated during high frequency deep brain stimulation (HF DBS) in a patient with DYT3+ dystonia and in a patient with secondary dystonia due to childhood encephalitis., Materials and Methods: We recorded local field potentials from the DBS lead in the GPi of four patients (seven hemispheres) with secondary dystonia and from one patient (two hemispheres) with primary DYT3+ dystonia. In two patients, we also recorded pallidal local field potentials during the administration of 10 sec epochs of HF DBS., Results: Power spectral densities during rest demonstrated visible peaks in the beta band in seven out of nine cases. In DYT3+ dystonia, power in the alpha and beta bands, but not theta band, was attenuated during HF DBS in the GPe and in GPi, and attenuation was most prominent in the high beta band. This patient demonstrated an early and maintained improvement in dystonia. There was no beta peak and the power spectrum was not attenuated during HF DBS in a patient with secondary dystonia due to childhood encephalitis., Conclusions: These results suggest that beta hypersynchrony, demonstrated now in both primary and secondary dystonia, may play a pathophysiological role in pathological hyperkinesis. Further investigation is needed in a larger cohort of well-characterized primary and secondary dystonia patients., (© 2012 International Neuromodulation Society.)
- Published
- 2013
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16. A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations.
- Author
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Chen DH, Raskind WH, Parson WW, Sonnen JA, Vu T, Zheng Y, Matsushita M, Wolff J, Lipe H, and Bird TD
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Exons genetics, Female, Gait Disorders, Neurologic pathology, Gait Disorders, Neurologic physiopathology, Genetic Diseases, X-Linked physiopathology, Genetic Linkage genetics, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Immunohistochemistry, Infant, Intracellular Signaling Peptides and Proteins metabolism, LIM Domain Proteins, LIM-Homeodomain Proteins, Male, Middle Aged, Models, Molecular, Muscle Proteins metabolism, Muscle, Skeletal metabolism, Muscular Atrophy, Spinal physiopathology, Mutation genetics, Mutation physiology, Mutation, Missense genetics, Pedigree, Phenotype, Polymorphism, Single Nucleotide genetics, Protein Conformation, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Young Adult, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked pathology, Intracellular Signaling Peptides and Proteins genetics, Muscle Proteins genetics, Muscular Atrophy, Spinal genetics, Muscular Atrophy, Spinal pathology
- Abstract
An X-linked myopathy was recently associated with mutations in the four-and-a-half-LIM domains 1 (FHL1) gene. We identified a family with late onset, slowly progressive weakness of scapuloperoneal muscles in three brothers and their mother. A novel missense mutation in the LIM2 domain of FHL1 (W122C) co-segregated with disease in the family. The phenotype was less severe than that in other reported families. Muscle biopsy revealed myopathic changes with FHL1 inclusions that were ubiquitin- and desmin-positive. This mutation provides additional evidence for X-linked myopathy caused by a narrow spectrum of mutations in FHL1, mostly in the LIM2 domain. Molecular dynamics (MD) simulations of the newly identified mutation and five previously published missense mutations in the LIM2 domain revealed no major distortions of the protein structure or disruption of zinc binding. There were, however, increases in the nonpolar, solvent-accessible surface area in one or both of two clusters of residues, suggesting that the mutant proteins have a variably increased propensity to aggregate. Review of the literature shows a wide range of phenotypes associated with mutations in FHL1. However, recognizing the typical scapuloperoneal phenotype and X-linked inheritance pattern will help clinicians arrive at the correct diagnosis., (Published by Elsevier B.V.)
- Published
- 2010
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17. B cell-specific lentiviral gene therapy leads to sustained B-cell functional recovery in a murine model of X-linked agammaglobulinemia.
- Author
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Kerns HM, Ryu BY, Stirling BV, Sather BD, Astrakhan A, Humblet-Baron S, Liggitt D, and Rawlings DJ
- Subjects
- Agammaglobulinaemia Tyrosine Kinase, Animals, B-Lymphocytes cytology, Bone Marrow Cells cytology, Bone Marrow Transplantation, CD79 Antigens genetics, Cell Line, Cell Lineage, Disease Models, Animal, Genetic Diseases, X-Linked physiopathology, Genetic Vectors genetics, Humans, Immunoglobulin Heavy Chains genetics, Mice, Mice, Inbred C57BL, Organ Specificity genetics, Protein-Tyrosine Kinases deficiency, Protein-Tyrosine Kinases metabolism, Protein-Tyrosine Kinases therapeutic use, Agammaglobulinemia physiopathology, Agammaglobulinemia therapy, B-Lymphocytes physiology, Genetic Diseases, X-Linked therapy, Genetic Therapy adverse effects, Lentivirus genetics, Recovery of Function physiology
- Abstract
The immunodeficiency disorder, X-linked agammaglobulinemia (XLA), results from mutations in the gene encoding Bruton tyrosine kinase (Btk). Btk is required for pre-B cell clonal expansion and B-cell antigen receptor signaling. XLA patients lack mature B cells and immunoglobulin and experience recurrent bacterial infections only partially mitigated by life-long antibody replacement therapy. In pursuit of definitive therapy for XLA, we tested ex vivo gene therapy using a lentiviral vector (LV) containing the immunoglobulin enhancer (Emu) and Igbeta (B29) minimal promoter to drive B lineage-specific human Btk expression in Btk/Tec(-/-) mice, a strain that reproduces the features of human XLA. After transplantation of EmuB29-Btk-LV-transduced stem cells, treated mice showed significant, albeit incomplete, rescue of mature B cells in the bone marrow, peripheral blood, spleen, and peritoneal cavity, and improved responses to T-independent and T-dependent antigens. LV-treated B cells exhibited enhanced B-cell antigen receptor signaling and an in vivo selective advantage in the peripheral versus central B-cell compartment. Secondary transplantation showed sustained Btk expression, viral integration, and partial functional responses, consistent with long-term stem cell marking; and serial transplantation revealed no evidence for cellular or systemic toxicity. These findings strongly support pursuit of B lineage-targeted LV gene therapy in human XLA.
- Published
- 2010
- Full Text
- View/download PDF
18. Lines of Blaschko and choroideremia.
- Author
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MacDonald IM, Sui R, and Zein W
- Subjects
- Choroideremia diagnosis, Choroideremia genetics, Electroretinography, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked physiopathology, Humans, Retinal Cone Photoreceptor Cells physiology, Visual Fields, Choroideremia physiopathology, Heterozygote, Mosaicism, Psychophysics methods, Retina physiopathology
- Published
- 2009
- Full Text
- View/download PDF
19. Persistent CNS dysfunction in a boy with CMT1X.
- Author
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Siskind C, Feely SM, Bernes S, Shy ME, and Garbern JY
- Subjects
- Adult, Ataxia genetics, Brain pathology, Charcot-Marie-Tooth Disease genetics, Charcot-Marie-Tooth Disease pathology, Child, Preschool, Connexins genetics, DNA Mutational Analysis, Dysarthria genetics, Female, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked pathology, Humans, Language Disorders genetics, Language Disorders physiopathology, Magnetic Resonance Imaging, Male, Mothers, Muscle Weakness genetics, Muscle Weakness physiopathology, Mutation, Missense, Neural Conduction, Gap Junction beta-1 Protein, Ataxia physiopathology, Charcot-Marie-Tooth Disease physiopathology, Dysarthria physiopathology, Genetic Diseases, X-Linked physiopathology
- Abstract
Objective: X-linked Charcot Marie Tooth disease (CMT1X) is a hereditary demyelinating neuropathy caused by mutations in the GJB1 gene encoding the gap junction protein connexin 32 (Cx32). Some GJB1 mutations have been reported to cause transient clinical CNS dysfunction. We report a boy with persistent CNS abnormalities possibly caused by CMT1X., Methods: A five year old boy was evaluated by clinical, electrophysiological, MRI and genetic testing., Results: The patient's early motor milestones were normal to age 5 months. His subsequent course was one of slow improvement punctuated by brief periods of loss of ability to sit between age 5 and 10 months, loss of language between 12 months and 2 years and 1 episode of non-clinically observed resolved left-sided facial weakness. At age 5, he had truncal instability, appendicular ataxia, and dysarthric speech. Cognition was normal. He had mild toe weakness and intrinsic muscle atrophy. MRI evaluation was abnormal. Electrophysiologic testing revealed slowed motor conduction velocities and sensory responses of low amplitude. Genetic workup was normal excepting a novel missense mutation in GJB1, causing a p.54N>H substitution., Conclusion: The patient has persistent CNS abnormalities characterized by dysarthria and ataxia. These are similar to transient CNS abnormalities reported in patients with CMT1X. These CNS findings may be the direct result of his novel Cx32 mutation.
- Published
- 2009
- Full Text
- View/download PDF
20. Cardiac abnormalities in McLeod syndrome.
- Author
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Oechslin E, Kaup D, Jenni R, and Jung HH
- Subjects
- Adult, Cardiomyopathies pathology, Cardiomyopathies physiopathology, Fatal Outcome, Female, Genetic Diseases, X-Linked pathology, Genetic Diseases, X-Linked physiopathology, Heart Ventricles pathology, Humans, Male, Middle Aged, Neuroacanthocytosis pathology, Neuroacanthocytosis physiopathology, Stroke Volume, Ventricular Dysfunction, Left pathology, Ventricular Dysfunction, Left physiopathology, Ventricular Function, Left, Cardiomyopathies genetics, Death, Sudden, Cardiac, Genetic Diseases, X-Linked genetics, Neuroacanthocytosis genetics, Ventricular Dysfunction, Left genetics
- Abstract
We report the cardiac features of seven patients with X-linked McLeod neuroacanthocytosis syndrome, a multi-system disorder resembling Huntington's disease and cardiac manifestations in about half of the patients reported to date. One patient presented with a cardiomyopathy (normal size of the left ventricle with concentric remodeling and mildly impaired ejection fraction, 43%). This patient died from sudden cardiac death in the absence of any cardiovascular risk factors. Autopsy demonstrated eccentric hypertrophy and mild left ventricular dilatation. Histopathology was not specific and revealed focal myocyte hypertrophy, slight variation of myofiber size and patchy interstitial fibrosis.
- Published
- 2009
- Full Text
- View/download PDF
21. Lines of Blaschko.
- Author
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Meyer CH, Rodrigues EB, and Kroll P
- Subjects
- Choroideremia diagnosis, Choroideremia genetics, Electroretinography, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked physiopathology, Heterozygote, Humans, Mosaicism, Psychophysics methods, Retinal Cone Photoreceptor Cells physiopathology, Visual Fields, Choroideremia physiopathology, Retina physiopathology
- Published
- 2008
- Full Text
- View/download PDF
22. X-linked retinoschisis.
- Author
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Byeon SH, Kwon OW, and Lee SC
- Subjects
- Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked physiopathology, Humans, Postoperative Period, Retinoschisis diagnosis, Retinoschisis physiopathology, Tomography, Optical Coherence, Treatment Outcome, Visual Acuity, Genetic Diseases, X-Linked surgery, Retinoschisis genetics, Retinoschisis surgery, Vitrectomy
- Published
- 2008
- Full Text
- View/download PDF
23. Correlation of ophthalmic examination with carrier status in females potentially harboring a severe Norrie disease gene mutation.
- Author
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Khan AO, Aldahmesh MA, and Meyer B
- Subjects
- Cysteine, Female, Genes, Recessive, Genetic Diseases, X-Linked physiopathology, Hearing Loss, Sensorineural physiopathology, Humans, Intellectual Disability psychology, Male, Molecular Biology, Pedigree, Phenylalanine, Prospective Studies, Retinal Diseases diagnosis, Retinal Diseases genetics, Severity of Illness Index, Vitreoretinopathy, Proliferative diagnosis, Vitreoretinopathy, Proliferative physiopathology, Diagnostic Techniques, Ophthalmological, Eye Proteins genetics, Genetic Diseases, X-Linked genetics, Hearing Loss, Sensorineural genetics, Heterozygote, Intellectual Disability genetics, Mutation, Nerve Tissue Proteins genetics, Vitreoretinopathy, Proliferative genetics
- Abstract
Purpose: To correlate ophthalmic findings with carrier status for a severe Norrie disease (ND) gene mutation (C95F)., Design: Prospective interventional case series., Participants: Six potential carriers and 1 obligate carrier from a family harboring the mutation., Methods: An ophthalmologist blind to the pedigree performed a full ophthalmic examination for the 7 asymptomatic family members. A peripheral blood sample was collected from each for ND gene sequencing., Main Outcome Measures: Ophthalmic examination findings (with attention to the presence or absence of retinal findings) and results of ND gene sequencing., Results: Three carriers were identified by molecular genetics, and all 3 of them had peripheral retinal abnormality. However, 3 of the 4 genetically identified noncarriers also exhibited peripheral retinal abnormality. Two of these noncarriers with retinal findings were the offspring of a confirmed noncarrier. The genetically identified noncarrier with a normal peripheral retinal examination was the daughter of an obligate carrier., Conclusions: The presence of peripheral retinal changes was not useful for carrier prediction in a family harboring ND. There are likely additional loci responsible for phenotypic expression.
- Published
- 2008
- Full Text
- View/download PDF
24. Detection of mosaic retinal dysfunction in choroideremia carriers electroretinographic and psychophysical testing.
- Author
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Vajaranant TS, Fishman GA, Szlyk JP, Grant-Jordan P, Lindeman M, and Seiple W
- Subjects
- Adult, Aged, Choroideremia diagnosis, Choroideremia genetics, Cohort Studies, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked physiopathology, Humans, Middle Aged, Prospective Studies, Retinal Cone Photoreceptor Cells physiopathology, Visual Fields, Choroideremia physiopathology, Electroretinography, Heterozygote, Mosaicism, Psychophysics methods, Retina physiopathology
- Abstract
Purpose: To test whether choroideremia carriers have a mosaic pattern of retinal dysfunction, as noted in carriers of X-linked recessive retinitis pigmentosa and X-linked retinoschisis., Design: Prospective observational case series., Participants: Seven obligate choroideremia carriers (age range, 18-72) with visual acuity (VA) of 20/25 or better were recruited into the study., Methods: The carriers underwent VA testing (Snellen chart), ophthalmic examination, Humphrey visual field (VF), and multifocal electroretinographic testing. The amplitude and implicit time scales were measured by the algorithm of Hood and Li. The amplitude measures (a scales) and implicit time measures (t scales) were reported abnormal when they were >2 standard deviations above the mean of age-similar normally sighted control subjects., Main Outcome Measures: Mapping of local 103 electroretinographic response amplitudes and implicit times., Results: Only 1 of the 7 carriers showed abnormal Humphrey VF thresholds, whereas 6 of the 7 carriers showed a mosaic pattern of retinal dysfunction measured by multifocal electroretinographic testing. All 6 carriers showed statistically significant implicit time delays, whereas 4 carriers showed statistically significant amplitude reductions and implicit time delays (P<0.05 to P<0.0006). One carrier with a normal-appearing macula and normal Humphrey VF showed a cluster of statistically significant implicit time delays within the macula (P<0.05 to P<0.0006). The overall extent of local electroretinographic abnormalities corresponded to the severity of ophthalmoscopically apparent pigmentary changes. The one carrier with mild threshold elevation on Humphrey VF testing showed the most ophthalmoscopically apparent extensive fundus pigmentary changes., Conclusions: We demonstrated a mosaic pattern of retinal cone dysfunction in carriers of choroideremia. Our findings are consistent with the Lyon hypothesis of random X-chromosome inactivation. Multifocal electroretinographic testing is potentially sensitive to detect local retinal dysfunction in choroideremia carriers even in those with a normal-appearing macula and good VA.
- Published
- 2008
- Full Text
- View/download PDF
25. Resolution of retinoschisis after vitreous surgery in X-linked retinoschisis.
- Author
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Ikeda F, Iida T, and Kishi S
- Subjects
- Adolescent, Adult, Child, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked physiopathology, Humans, Male, Postoperative Period, Retinoschisis diagnosis, Retinoschisis physiopathology, Retrospective Studies, Tomography, Optical Coherence, Treatment Outcome, Visual Acuity, Genetic Diseases, X-Linked surgery, Retinoschisis genetics, Retinoschisis surgery, Vitrectomy
- Abstract
Purpose: To describe the efficacy of vitreous surgery to treat X-linked retinoschisis., Design: Retrospective, comparative, interventional case series., Participants: Three patients (5 eyes) had foveal retinoschisis with peripheral retinoschisis. The patients' ages were 26, 7, and 17 years at the first surgery. The preoperative best-corrected visual acuity (BCVA) was 20/100 and 20/40 in patient 1, 20/30 in patient 2, and 20/100 and 20/200 in patient 3., Methods: The vitreous surgery consisted of core vitrectomy, surgically induced posterior vitreous detachment (PVD), removal of the internal limiting membrane (except for the right eye of patient 1), and 30% sulfur hexafluoride gas tamponade. The follow-up periods ranged from 6 months to 12 years., Main Outcome Measures: Best-corrected visual acuity and retinal tomography monitored by optical coherence tomography., Results: Restoration of the foveal depression with collapse of the schisis cavity was achieved with the first surgery in 4 (80%) of the 5 eyes. In the right eye of patient 1, the retinoschisis persisted after the first surgery because of failed surgically induced PVD; the retinoschisis resolved promptly after the second surgery with successful induction of PVD. The BCVA improved in 3 eyes and was unchanged in 2 eyes., Conclusions: Vitreous surgery resulted in reattachment of the retinoschisis with visual improvement. Vitreous traction may play a role in the development of foveal retinoschisis.
- Published
- 2008
- Full Text
- View/download PDF
26. X-linked cone dysfunction syndrome with myopia and protanopia.
- Author
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Michaelides M, Johnson S, Bradshaw K, Holder GE, Simunovic MP, Mollon JD, Moore AT, and Hunt DM
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Chromosomes, Human, X genetics, Color Vision Defects physiopathology, DNA Mutational Analysis, Electroretinography, Genetic Diseases, X-Linked physiopathology, Humans, Male, Myopia physiopathology, Pedigree, Polymerase Chain Reaction, Rod Opsins genetics, Syndrome, Color Vision Defects genetics, Genetic Diseases, X-Linked genetics, Myopia genetics, Retinal Cone Photoreceptor Cells physiopathology
- Abstract
Purpose: To perform a detailed clinical, psychophysical, and molecular assessment of members of 4 families with an unusual X-linked cone dysfunction syndrome associated with myopia., Participants: Affected and unaffected members of 4 British nonconsanguineous families., Methods: Subjects underwent both detailed clinical examination and psychophysical testing. After informed consent was obtained, blood samples were taken for DNA extraction, and molecular genetic analysis was performed. The strategy for molecular analysis was to amplify the coding regions of the long and middle wavelength-sensitive cone opsin genes and the upstream locus control region by polymerase chain reaction and to examine these fragments for mutations by sequencing of DNA., Results: The phenotype was almost identical in all 4 families, consisting of moderate to high myopia, astigmatism, moderately reduced acuity, and normal fundi. Electroretinography showed abnormal cone but normal rod responses. Psychophysical testing showed a selective impairment of long cones in combination with well-preserved middle cone and short cone function. There was no evidence to suggest that the phenotype was progressive. Molecular analysis of the X-linked opsin gene array in the 4 families indicated that affected males have inherited the same X-chromosome from their mother. In 2 families, a long/middle hybrid gene was detected. In a third family, the commonly described deleterious Cys203Arg amino acid substitution was identified in both the long and middle opsin genes. In the fourth family, the only abnormality was absence of a middle opsin exon 2; the cause of the protanopia in this family is uncertain., Conclusions: The X-linked cone dysfunction syndrome associated with myopia and dichromacy described here has many similarities to Bornholm eye disease, a condition previously mapped to Xq28. Except for the Cys203Arg substitution in one family, no alterations in the opsin gene array were identified that could underlie the cone dysfunction. It is therefore possible that the cone dysfunction may have a genetic origin different from that of the dichromacy.
- Published
- 2005
- Full Text
- View/download PDF
27. Muscle MRI findings of X-linked spinal and bulbar muscular atrophy.
- Author
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Hamano T, Mutoh T, Hirayama M, Kawamura Y, Nagata M, Fujiyama J, and Kuriyama M
- Subjects
- Disease Progression, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked physiopathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Muscle, Skeletal innervation, Muscle, Skeletal physiopathology, Muscular Atrophy etiology, Muscular Atrophy physiopathology, Muscular Atrophy, Spinal genetics, Muscular Atrophy, Spinal physiopathology, Predictive Value of Tests, Thigh physiopathology, Genetic Diseases, X-Linked diagnosis, Muscle, Skeletal pathology, Muscular Atrophy diagnosis, Muscular Atrophy, Spinal diagnosis, Thigh pathology
- Abstract
We report here muscle MRI findings of the lower limb in X-linked spinal and bulbar muscular atrophy (SBMA). T1-weighted imaging of muscle MRI disclosed that the thigh muscles, including the semimembranosus, biceps femoris longus and the vastus lateralis muscles, showed high intensity signals with atrophy. Contrarily, the sartorius, gracilis and rectus femoris muscles were comparably preserved. Not only the thigh muscles, but also the calf muscles including the gastrocnemius medialis and lateralis, and soleus muscles showed high intensity signals. In amyotrophic lateral sclerosis (ALS), the leg muscles are generally atrophic, but the selective pattern of fatty degeneration, seen in SBMA was not observed. Muscle MRI is a useful method of estimating the distribution and severity of SBMA in affected muscles.
- Published
- 2004
- Full Text
- View/download PDF
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