排序方式: 共有86条查询结果,搜索用时 15 毫秒
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Ji Yun Song Puya Aravand Sergei Nikonov Lanfranco Leo Arkady Lyubarsky Jeannette L. Bennicelli Jieyan Pan Zhangyong Wei Ivan Shpylchak Pamela Herrera Daniel J. Bennett Nicoletta Commins Albert M. Maguire Jennifer Pham Anneke I. den Hollander Frans P.M. Cremers Robert K. Koenekoop Ronald Roepman Jean Bennett 《Molecular therapy》2018,26(6):1581-1593
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Inga Ebermann Jennifer B. Phillips Max C. Liebau Robert K. Koenekoop Bernhard Schermer Irma Lopez Ellen Sch?fer Anne-Francoise Roux Claudia Dafinger Antje Bernd Eberhart Zrenner Mireille Claustres Bernardo Blanco Gudrun Nürnberg Peter Nürnberg Rebecca Ruland Monte Westerfield Thomas Benzing Hanno J. Bolz 《The Journal of clinical investigation》2010,120(6):1812-1823
Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease. 相似文献
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Sharola Dharmaraj Ban P. Leroy Melanie M. Sohocki Robert K. Koenekoop Isabelle Perrault Khalid Anwar Shagufta Khaliq R. Summathi Devi David G. Birch Elaine De Pool Natalio Izquierdo Lionel Van Maldergem Mohammad Ismail Annette M. Payne Graham E. Holder Shomi S. Bhattacharya Alan C. Bird Josseline Kaplan Irene H. Maumenee 刘欣怡 《美国医学会眼科杂志(中文版)》2005,17(2):119-120
目的:叙述26例先证者中芳香族羟基碳氢化合物受体蛋白样1蛋白质(AIPL1)突变的先天性Leber黑蒙(LCA)的表现型,并比较其他LCA相关性基因的表现型。叙述杂合子携带者的视网膜电图(ERG)。 相似文献
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A missense mutation in GUCY2D acts as a genetic modifier in RPE65-related Leber Congenital Amaurosis
Silva E Dharmaraj S Li YY Pina AL Carter RC Loyer M Traboulsi E Theodossiadis G Koenekoop R Sundin O Maumenee I 《Ophthalmic genetics》2004,25(3):205-217
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. 相似文献
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Koenekoop RK 《Survey of ophthalmology》2004,49(4):379-398
Leber congenital amaurosis is a congenital retinal dystrophy described almost 150 years ago. Today, Leber congenital amaurosis is proving instrumental in our understanding of the molecular events that determine normal and aberrant retinal development. Six genes have been shown to be mutated in Leber congenital amaurosis, and they participate in a wide variety of retinal pathways: retinoid metabolism (RPE65), phototransduction (GUCY2D), photoreceptor outer segment development (CRX), disk morphogenesis (RPGRIP1), zonula adherens formation (CRB1), and cell-cycle progression (AIPL1). Longitudinal studies of visual performance show that most Leber congenital amaurosis patients remain stable, some deteriorate, and rare cases exhibit improvements. Histopathological analyses reveal that most cases have extensive degenerative retinal changes, some have an entirely normal retinal architecture, whereas others have primitive, poorly developed retinas. Animal models of Leber congenital amaurosis have greatly added to understanding the impact of the genetic defects on retinal cell death, and response to rescue. Gene therapy for RPE65 deficient dogs partially restored sight, and provides the first real hope of treatment for this devastating blinding condition. 相似文献
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Rufiange M Dassa J Dembinska O Koenekoop RK Little JM Polomeno RC Dumont M Chemtob S Lachapelle P 《Vision research》2003,43(12):1405-1412
With progressively brighter stimuli, the amplitude of the photopic b-wave first increases, briefly saturates and then decreases gradually to reach a plateau, where the amplitude of the b-wave equals that of the a-wave; a phenomenon previously presented as the photopic hill. The unique presentation of this luminance-response function seriously complicates its analysis with curve fitting equations such as that of Naka-Rushton used for scotopic electroretinogram. We report a method of analysis of the photopic hill based on easily identifiable and reproducible features of the ascending and descending limbs of this function. The clinical usefulness of these parameters is illustrated with selected cases of retinal disorders. 相似文献
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Sniderman LC Koenekoop RK O'Gorman AM Usher RH Sufrategui MR Moroz B Watters GV Der Kaloustian VM 《American journal of medical genetics》2000,90(2):146-149
We report on a 4-year-old boy with Knobloch syndrome. He has vitreoretinal degeneration, high myopia, cataract, telecanthus, hypertelorism, and a high-arched palate. He also has a defect of the anterior midline scalp with involvement of the frontal bone as documented by a computed tomography (CT) scan. The brain was normal on CT scan and magnetic resonance imaging. We present a review of the 23 published cases with this syndrome. Our patient illustrates the importance of investigating for underlying ocular and central nervous system pathology whenever midline scalp defects are present. 相似文献