The Experts below are selected from a list of 741 Experts worldwide ranked by ideXlab platform
Nagahisa Yoshimura - One of the best experts on this subject based on the ideXlab platform.
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A case of WAGR Syndrome in association with developmental glaucoma requiring bilateral Baerveldt glaucoma implants and subsequent tube repositioning.
Clinical Ophthalmology, 2015Co-Authors: Tadamichi Akagi, Munemitsu Yoshikawa, Hideo Nakanishi, Nagahisa YoshimuraAbstract:Glaucoma drainage device implantation is efficacious for the treatment of pediatric glaucoma patients when multiple angle surgeries fail. However, tube touching of the corneal endothelium is one of the major postoperative complications to deal with. A 15-month-old male patient with Wilms’ tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) Syndrome was diagnosed with bilateral developmental glaucoma. He underwent Baerveldt glaucoma implant (BGI) surgeries in both eyes after multiple failed trabeculotomies. The tube in his right eye was touching the cornea 15 months after BGI surgery. To avoid corneal endothelium damage, BGI tube repositioning with scleral fixation was performed without serious complications. The bilateral BGI surgeries achieved successful intraocular pressure reduction for over 2 years and tube repositioning with scleral fixation of BGI tube was successful for BGI tube malposition. Although careful attention to intraocular pressure and tube malposition is essential after glaucoma drainage device implantation, especially in pediatric cases, BGI surgery is effective in the management of developmental glaucoma following unsuccessful angle surgeries.
Mingyao Liu - One of the best experts on this subject based on the ideXlab platform.
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lgr4 gpr48 inactivation leads to aniridia genitourinary anomalies mental retardation Syndrome defects
Journal of Biological Chemistry, 2014Co-Authors: Jinsheng Weng, Stefan Siwko, Jian Luo, Mingyao LiuAbstract:AGR Syndrome (the clinical triad of aniridia, genitourinary anomalies, and mental retardation, a subgroup of WAGR Syndrome for Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation) is a rare Syndrome caused by a contiguous gene deletion in the 11p13-14 region. However, the mechanisms of WAGR Syndrome pathogenesis are elusive. In this study we provide evidence that LGR4 (also named GPR48), the only G-protein-coupled receptor gene in the human chromosome 11p12-11p14.4 fragment, is the key gene responsible for the diseases of AGR Syndrome. Deletion of Lgr4 in mouse led to aniridia, polycystic kidney disease, genitourinary anomalies, and mental retardation, similar to the pathological defects of AGR Syndrome. Furthermore, Lgr4 inactivation significantly increased cell apoptosis and decreased the expression of multiple important genes involved in the development of WAGR Syndrome related organs. Specifically, deletion of Lgr4 down-regulated the expression of histone demethylases Jmjd2a and Fbxl10 through cAMP-CREB signaling pathways both in mouse embryonic fibroblast cells and in urinary and reproductive system mouse tissues. Our data suggest that Lgr4, which regulates eye, kidney, testis, ovary, and uterine organ development as well as mental development through genetic and epigenetic surveillance, is a novel candidate gene for the pathogenesis of AGR Syndrome.
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LGR4/GPR48 inactivation leads to aniridia-genitourinary anomalies-mental retardation Syndrome defects.
The Journal of biological chemistry, 2014Co-Authors: Jinsheng Weng, Stefan Siwko, Jian Luo, Mingyao LiuAbstract:AGR Syndrome (the clinical triad of aniridia, genitourinary anomalies, and mental retardation, a subgroup of WAGR Syndrome for Wilm's tumor, aniridia, genitourinary anomalies, and mental retardation) is a rare Syndrome caused by a contiguous gene deletion in the 11p13-14 region. However, the mechanisms of WAGR Syndrome pathogenesis are elusive. In this study we provide evidence that LGR4 (also named GPR48), the only G-protein-coupled receptor gene in the human chromosome 11p12-11p14.4 fragment, is the key gene responsible for the diseases of AGR Syndrome. Deletion of Lgr4 in mouse led to aniridia, polycystic kidney disease, genitourinary anomalies, and mental retardation, similar to the pathological defects of AGR Syndrome. Furthermore, Lgr4 inactivation significantly increased cell apoptosis and decreased the expression of multiple important genes involved in the development of WAGR Syndrome related organs. Specifically, deletion of Lgr4 down-regulated the expression of histone demethylases Jmjd2a and Fbxl10 through cAMP-CREB signaling pathways both in mouse embryonic fibroblast cells and in urinary and reproductive system mouse tissues. Our data suggest that Lgr4, which regulates eye, kidney, testis, ovary, and uterine organ development as well as mental development through genetic and epigenetic surveillance, is a novel candidate gene for the pathogenesis of AGR Syndrome.
Tadamichi Akagi - One of the best experts on this subject based on the ideXlab platform.
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A case of WAGR Syndrome in association with developmental glaucoma requiring bilateral Baerveldt glaucoma implants and subsequent tube repositioning.
Clinical Ophthalmology, 2015Co-Authors: Tadamichi Akagi, Munemitsu Yoshikawa, Hideo Nakanishi, Nagahisa YoshimuraAbstract:Glaucoma drainage device implantation is efficacious for the treatment of pediatric glaucoma patients when multiple angle surgeries fail. However, tube touching of the corneal endothelium is one of the major postoperative complications to deal with. A 15-month-old male patient with Wilms’ tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) Syndrome was diagnosed with bilateral developmental glaucoma. He underwent Baerveldt glaucoma implant (BGI) surgeries in both eyes after multiple failed trabeculotomies. The tube in his right eye was touching the cornea 15 months after BGI surgery. To avoid corneal endothelium damage, BGI tube repositioning with scleral fixation was performed without serious complications. The bilateral BGI surgeries achieved successful intraocular pressure reduction for over 2 years and tube repositioning with scleral fixation of BGI tube was successful for BGI tube malposition. Although careful attention to intraocular pressure and tube malposition is essential after glaucoma drainage device implantation, especially in pediatric cases, BGI surgery is effective in the management of developmental glaucoma following unsuccessful angle surgeries.
Hiroyuki Torisu - One of the best experts on this subject based on the ideXlab platform.
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Sustained endocrine profiles of a girl with WAGR Syndrome.
BMC medical genetics, 2017Co-Authors: Yui Takada, Yasunari Sakai, Yuki Matsushita, Kazuhiro Ohkubo, Yuhki Koga, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Masafumi Sanefuji, Hiroyuki TorisuAbstract:Background Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) Syndrome is a rare genetic disorder caused by heterozygous deletions of WT1 and PAX6 at chromosome 11p13. Deletion of BDNF is known eto be associated with hyperphagia and obesity in both humans and animal models; however, neuroendocrine and epigenetic profiles of individuals with WAGR Syndrome remain to be determined.
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Sustained endocrine profiles of a girl with WAGR Syndrome
BMC, 2017Co-Authors: Yui Takada, Yasunari Sakai, Yuki Matsushita, Kazuhiro Ohkubo, Yuhki Koga, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Masafumi Sanefuji, Hiroyuki TorisuAbstract:Abstract Background Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) Syndrome is a rare genetic disorder caused by heterozygous deletions of WT1 and PAX6 at chromosome 11p13. Deletion of BDNF is known eto be associated with hyperphagia and obesity in both humans and animal models; however, neuroendocrine and epigenetic profiles of individuals with WAGR Syndrome remain to be determined. Case presentation We report a 5-year-old girl with the typical phenotype of WAGR Syndrome. She showed profound delays in physical growth, motor and cognitive development without signs of obesity. Array comparative genome hybridization (CGH) revealed that she carried a 14.4 Mb deletion at 11p14.3p12, encompassing the WT1, PAX6 and BDNF genes. She experienced recurrent hypoglycemic episodes at 5 years of age. Insulin tolerance and hormonal loading tests showed normal hypothalamic responses to the hypoglycemic condition and other stimulations. Methylation analysis for freshly prepared DNA from peripheral lymphocytes using the pyro-sequencing-based system showed normal patterns of methylation at known imprinting control regions. Conclusions Children with WAGR Syndrome may manifest profound delay in postnatal growth through unknown mechanisms. Epigenetic factors and growth-associated genes in WAGR Syndrome remain to be characterized
Daniel A. Haber - One of the best experts on this subject based on the ideXlab platform.
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Molecular Genetics of Wilms Tumor
Hematology Oncology Clinics of North America, 1995Co-Authors: Paul E. Grundy, Max J. Coppes, Daniel A. HaberAbstract:The study of Wilms tumor-predisposing congenital Syndromes has led to the identification of one tumor-suppressor gene, WT1, and to the localization of WT2. Molecular genetic analyses of these and sporadic Wilms tumors have clarified the role of WT1 in Wilms tumor with aniridia, genitourinary malformations, and mental retardation (WAGR)-Syndrome patients, but much remains unclear in the case of WT2 and the Beckwith-Wiedemann Syndrome. Loci on chromosomes 16q and 1p have now been implicated in the progression of Wilms tumor and may serve as molecular prognostic markers. It is now clear that Wilms tumors are genetically heterogeneous and may be multigenic in origin. Molecular analyses can now be used for genetic counseling in some children and may become useful in individualizing therapy.
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Altered trans-Activational Properties of a Mutated WT1 Gene Product in a WAGR-associated Wilms' Tumor
Cancer research, 1993Co-Authors: Seon Park, Gail E. Tomlinson, Perry D. Nisen, Daniel A. HaberAbstract:Abstract WAGR Syndrome is an acronym for a rare constellation of congenital abnormalities including predisposition to Wilms9 tumor, Aniridia, Genitourinary malformations, and mental Retardation. These congenital defects are associated with a constitutional deletion affecting one copy of chromosome band 11p13, implicating the loss of one allele from a number of contiguous genes in this Syndrome. Predisposition to Wilms9 tumor and genitourinary abnormalities have been attributed to hemizygosity for the WT1 tumor suppressor gene, a transcriptional repressor that is normally expressed transiently during kidney development. Here we show that a Wilms9 tumor arising in a child with WAGR Syndrome contained a point mutation within the remaining WT1 allele. This mutation resulted in a glycine to aspartic acid substitution within the putative trans-activation domain of WT1, converting the encoded protein from a transcriptional repressor to an activator of its target DNA sequence. Thus, a critical amino acid substitution can alter the functional properties of WT1 and provide the “second hit” required for Wilms tumorigenesis.
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WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour
Nature, 1991Co-Authors: Jerry Pelletier, Thomas M Glaser, Daniel A. Haber, Wendy Bruening, David E. HousmanAbstract:WILMS' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR Syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1,2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized3,4: it is expressed at high levels in the glomeruli of the kidney5, as well as the gonadal ridge of the developing gonad5, the Sertoli cells of the testis6 and the epithelial and granulosa cells of the ovary6, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.
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Familial predisposition to Wilms tumor does not segregate with the WT1 gene.
Genomics, 1991Co-Authors: Charles E. Schwartz, Daniel A. Haber, Vincent P. Stanton, Louise C. Strong, Mark H. Skolnick, David E. HousmanAbstract:Wilms tumor (WT) is one of the more common childhood cancers. A small fraction of WT occurs in association with aniridia, genitourinary abnormalities and mental retardation, the WAGR Syndrome, and these cases often are accompanied by a constitutional deletion of all or part of band 11p13. Recently a WT susceptibility gene (WT1), localized to 11p13, has been isolated and shown to be inactivated in some sporadic WTs. In the present study, a highly informative CA repeat polymorphism within the gene was studied in a family with six affected members in three generations. Predisposition to WT in this large family did not segregate with this polymorphism. Furthermore, linkage analysis indicated exclusion of WT predisposition from 11p15. These results provide definitive evidence that familial predisposition to WT can be mediated by a gene other than WT1.