The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
David N Louis - One of the best experts on this subject based on the ideXlab platform.
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long survival and therapeutic responses in patients with histologically disparate high grade gliomas demonstrating Chromosome 1p loss
Journal of Neurosurgery, 2000Co-Authors: Magdalena C Zlatescu, David R Macdonald, Sarah Jhung, Andreas Von Deimling, David N Louis, David A. Ramsay, Hikaru Sasaki, Anat Stemmerrachamimov, Gregory J CairncrossAbstract:Object. Allelic loss of Chromosome 1p is a powerful predictor of tumor chemosensitivity and prolonged survival in patients with anaplastic oligodendrogliomas. Chromosome 1p loss also occurs in astrocytic and oligoastrocytic gliomas, although less commonly than in pure oligodendroglial tumors. This observation raises the possibility investigated in this study that Chromosome 1p loss might also provide prognostic information for patients with high-grade gliomas with astrocytic components. Methods. The authors report on seven patients with high-grade gliomas composed of either pure astrocytic or mixed astrocytic-oligodendroglial phenotypes, who had remarkable neuroradiological responses to therapy or unexpectedly long survivals. All of the tumors from these seven patients demonstrated Chromosome 1p loss, whereas other genetic alterations characteristic of high-grade gliomas (p53 gene mutations, EGFR gene amplification, Chromosome 10 loss, Chromosome 19q loss, or CDKN2A/p16 deletions) were only found in occas...
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the human glia maturation factor gamma gene genomic structure and mutation analysis in gliomas with Chromosome 19q loss
Neurogenetics, 1999Co-Authors: Nils Peters, David N Louis, Justin S Smith, Issei Tachibana, Hyun K Lee, Ute Pohl, Bryce P Portier, Robert B JenkinsAbstract:Human glia maturation factor-gamma (hGMF-γ) is a recently identified gene that may be involved in glial differentiation, neural regeneration, and inhibition of tumor cell proliferation. The gene maps to the long arm of Chromosome 19 at band q13.2, a region that is frequently deleted in human malignant gliomas and is thus suspected to harbor a glioma tumor suppressor gene. Given the putative role of hGMF-γ in cell differentiation and proliferation and its localization to Chromosome 19q13, this gene is an interesting candidate for the Chromosome 19q glioma tumor suppressor gene. To evaluate this possibility, we determined the genomic structure of human hGMF-γ and performed mutation screening in a series of 41 gliomas with and without allelic loss of Chromosome 19q. Mutations were not detected, which suggests that hGMF-γ is not the Chromosome 19q glioma suppressor gene. However, the elucidation of the genomic structure of hGMF-γ may prove useful in future investigations of hGMF-γ in the normal adult and developing human nervous system.
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refined deletion mapping of the Chromosome 19q glioma tumor suppressor gene to the d19s412 std interval
Oncogene, 1996Co-Authors: Jonathan E Rosenberg, Andreas Von Deimling, David K Lisle, Jennifer A Burwick, Keisuke Ueki, Harvey W Mohrenweiser, David N LouisAbstract:: Allelic loss of chromsome 19q occurs frequently in malignant gliomas, suggesting the presence of a Chromosome 19q glioma tumor suppressor gene. Deletion mapping studies have delineated a 3.5 Mb candidate region between D19S219 and HRC. Cloned sequences from the proximal 425 kb of this interval, however, have not shown tumor-specific alterations. To refine the location of the tumor suppressor gene further, we conducted loss of heterozygosity studies on 191 malignant gliomas using nine PCR-based polymorphisms. These included the previously identified and physically mapped markers D19S219, DM, D19S112, HRC and the recently physically mapped polymorphisms at D19S412, STD, D19S596 and GYS. In addition, we isolated a novel microsatellite polymorphism that maps 400 kb telomeric to D19S112. Oligodendroglial tumors showed frequent loss of heterozygosity in all grades, and typically displayed allelic loss at all studied markers. Astrocytomas, however, showed frequent loss primarily in anaplastic astrocytomas and displayed deletion breakpoints within the candidate region. Deletion mapping revealed a minimal region of overlap between D19S412 and STD, a distance of 900 kb. These data suggest that the D19S412-STD interval represents the most likely location for a chromsome 19q glioma tumor suppressor gene involved in astrocytoma, and perhaps oligodendroglioma, tumorigenesis.
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Chromosome 19q deletions in human gliomas overlap telomeric to d19s219 and may target a 425 kb region centromeric to d19s112
Journal of Neuropathology and Experimental Neurology, 1995Co-Authors: William H Yong, Keisuke Ueki, Harvey W Mohrenweiser, James F Gusella, Andreas Von Deimling, Dean Chou, Griffith R Harsh, David N LouisAbstract:Chromosome 19q harbors a tumor suppressor gene that is involved in astrocytoma, oligodendroglioma and mixed glioma tumorigenesis. We had previously mapped this gene to an approximately 5 megabase region of Chromosome 19q13.2-13.3 between APOC2 and HRC. To narrow the location of this tumor suppressor further, we studied 138 gliomas for loss of allelic heterozygosity at six microsatellite polymorphisms between APOC2 and HRC, including a newly described polymorphism in the ERCC2 gene. Allelic loss occurred in 48 gliomas (35%), including 25 of 41 oligodendroglial tumors (61%). Four cases had proximal breakpoints within the APOC2-HRC region, two telomeric to ERCC2 and two telomeric to D19S219. In addition, one of the latter tumors had an interstitial deletion between D19S219 and D19S112, a distance of only 425 kilobases surrounding the DM (myotonic dystrophy) gene. These findings suggest that the glioma tumor suppressor on Chromosome 19q maps to 19q13.3, telomeric to D19S219 and perhaps centromeric to D19S112. The data exclude a number of candidate genes from 19q13.2-13.3, including a putative phosphatase gene and the DNA repair/metabolism genes ERCC1, ERCC2 and probably LIG1.
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the putative glioma tumor suppressor gene on Chromosome 19q maps between apoc2 and hrc
Cancer Research, 1994Co-Authors: Mari Paz Rubio, Keisuke Ueki, Harvey W Mohrenweiser, Katia M Correa, James F Gusella, Andreas Von Deimling, David N LouisAbstract:The frequent allelic loss of Chromosome 19q in human gliomas suggests that 19q harbors a tumor suppressor gene that is integral to glioma tumorigenesis. Our initial deletion mapping of this gene localized the common region of deletion to the distal long arm, 19q13.2-13.4. To bracket the putative tumor suppressor gene further, we have studied this region in 55 gliomas, using loss of heterozygosity studies for 11 well mapped, highly informative microsatellite polymorphisms that cover this area: D19S178; BCL3; APOC2; ERCC1; DM; D19S112; HRC; D19S246; KLK; D19S180; and D19S254 (from centromeric to telomeric). Twenty astrocytic, oligodendroglial, and mixed gliomas had deletions affecting this region. Of nine partial deletions, two cases maintained heterozygosity at APOC2 while showing allelic loss at the more telomeric markers, ERCC1 and DM, while five cases maintained heterozygosity at HRC but lost the more centromeric markers, D19S112 and DM. Nine cases lost the entire D19S178 to D19S254 region. Three astrocytic gliomas, including one with an interstitial deletion, had terminal deletions of 19q13.4. The minimum area of overlap shared by the interstitial deletions is between APOC2 and HRC, including ERCC1, DM, and D19S112. These findings suggest that the glioma tumor suppressor gene maps to an approximately 8-cM/5-megabase region on 19q13.2-13.3 between the proximal marker APOC2 and the distal marker HRC. Among the DNA repair/DNA metabolism genes on Chromosome 19q, ERCC1, LIG1, and perhaps ERCC2 are within the common area of deletion; XRCC1 is centromeric and is therefore excluded as a candidate.
Richard J.h. Smith - One of the best experts on this subject based on the ideXlab platform.
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split hand split foot malformation associated with sensorineural deafness inner and middle ear malformation hypodontia congenital vertical talus and deletion of eight microsatellite markers in 7q21 1 q21 3
Journal of Medical Genetics, 2001Co-Authors: E Haberlandt, Judith Loffler, Almut Hirststadlmann, Bernd Stockl, Peter Heinzerian, Werner Judmaier, Gerd Utermann, H Fischer, Thomas Müller, Richard J.h. SmithAbstract:Editor—The split hand/split foot malformation (SHFM, MIM 183600) is a central reduction defect of the hands and feet and occurs both as an isolated malformation and as part of several syndromes including the EEC syndrome (MIM 129900). We report on a 2 year old boy with SHFM associated with features of ectodermal hypoplasia, a submucous cleft palate, congenital vertical talus, malformations of the middle ear, profound sensorineural hearing loss resulting from Mondini dysplasia, and a de novo deletion of the paternal Chromosome 7q21.1-q21.3. This patient with syndromic SHFM represents a case of atypical EEC syndrome, but also displays abnormalities previously not associated with SHFM or EEC syndrome. The classical features of the autosomal dominant inherited EEC syndrome are ectrodactyly, ectodermal dysplasia, and clefting of the lip/palate. In most patients, there are additional anomalies typically affecting the urogenital and lacrimal systems.1 2 Some patients also have dysmorphic facies, a tendency to infectious disease, endocrine disorders, and mental retardation. This phenotypic variability has become increasingly apparent over the last 15 years3 4 and numerous related and overlapping syndromes have been delineated by many investigators.5 In an attempt to clarify classification, major and minor criteria for the diagnosis of EEC syndrome have been elaborated.3 4 Dominant inheritance of EEC has been documented in several large multigenerational families.6 At least 15 patients have been reported to have cytogenetic abnormalities of Chromosome 7q21.2-7q22.1, including nine patients with interstitial deletions.7-9 In addition, mutations in the gene encoding the transactivation factor p63 on Chromosome 3q27 have been identified in familial and sporadic cases of EEC syndrome.10 A third locus was mapped to Chromosome 19q,11 further delineating the genetic heterogeneity of this syndrome. The reason for the phenotypic heterogeneity in EEC syndrome patients with 7q abnormalities is unclear …
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split hand split foot malformation associated with sensorineural deafness inner and middle ear malformation hypodontia congenital vertical talus and deletion of eight microsatellite markers in 7q21 1 q21 3
Journal of Medical Genetics, 2001Co-Authors: E Haberlandt, Judith Loffler, Almut Hirststadlmann, Bernd Stockl, Peter Heinzerian, Werner Judmaier, Gerd Utermann, H Fischer, Thomas Müller, Richard J.h. SmithAbstract:Editor—The split hand/split foot malformation (SHFM, MIM 183600) is a central reduction defect of the hands and feet and occurs both as an isolated malformation and as part of several syndromes including the EEC syndrome (MIM 129900). We report on a 2 year old boy with SHFM associated with features of ectodermal hypoplasia, a submucous cleft palate, congenital vertical talus, malformations of the middle ear, profound sensorineural hearing loss resulting from Mondini dysplasia, and a de novo deletion of the paternal Chromosome 7q21.1-q21.3. This patient with syndromic SHFM represents a case of atypical EEC syndrome, but also displays abnormalities previously not associated with SHFM or EEC syndrome. The classical features of the autosomal dominant inherited EEC syndrome are ectrodactyly, ectodermal dysplasia, and clefting of the lip/palate. In most patients, there are additional anomalies typically affecting the urogenital and lacrimal systems.1 2 Some patients also have dysmorphic facies, a tendency to infectious disease, endocrine disorders, and mental retardation. This phenotypic variability has become increasingly apparent over the last 15 years3 4 and numerous related and overlapping syndromes have been delineated by many investigators.5 In an attempt to clarify classification, major and minor criteria for the diagnosis of EEC syndrome have been elaborated.3 4 Dominant inheritance of EEC has been documented in several large multigenerational families.6 At least 15 patients have been reported to have cytogenetic abnormalities of Chromosome 7q21.2-7q22.1, including nine patients with interstitial deletions.7-9 In addition, mutations in the gene encoding the transactivation factor p63 on Chromosome 3q27 have been identified in familial and sporadic cases of EEC syndrome.10 A third locus was mapped to Chromosome 19q,11 further delineating the genetic heterogeneity of this syndrome. The reason for the phenotypic heterogeneity in EEC syndrome patients with 7q abnormalities is unclear …
S S Bhattacharya - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 19q cone rod retinal dystrophy ocular phenotype
Archives of Ophthalmology, 1995Co-Authors: K Evans, S S Bhattacharya, Josephine Duvallyoung, Fred W Fitzke, Geoffrey B Arden, Alan C BirdAbstract:Objective: To describe the phenotype in a family with dominantly inherited cone-rod dystrophy with Chromosome assignment to a 19q locus, and to correlate this with current classifications of this retinal dystrophy. Design: A detailed clinical examination including Goldmann perimetry was undertaken in all family members. Six members under the age of 30 years underwent dark-adapted electroretinography, color contrast-sensitivity measurement, dark-adapted static perimetry, and dark adaptometry. Patients: The study included 34 affected and 22 unaffected patients in four generations of a pedigree that manifested autosomal dominant cone-rod retinal dystrophy linked to a Chromosome 19q locus by genetic linkage analysis. Results: Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than rod function. Conclusions: The phenotype associated with this mutation does not fit well into previous subtypes of conerod dystrophy. Further studies will be needed to correlate specific genetic mutations in this group of conditions with the various clinical phenotypes.
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refinement of the cone rod retinal dystrophy locus on Chromosome 19q
American Journal of Human Genetics, 1994Co-Authors: Cheryl Y Gregory, K Evans, Joanne Whittaker, Alan Fryer, J Weissenbach, S S BhattacharyaAbstract:Cone-rod dystrophy (CRD) is a severe example of an inherited retinal dystrophy: ophthalmic diseases that as a group constitute the commonest causes of blindness in children in the developed world and account for a significant proportion of visual handicap in adults. Two case reports suggested loci for CRD-causing genes on Chromosomes 18q and Chromosome 17q. Recently, we reported the results of a total genome search that localized an autosomal dominant form of CRD to Chromosome 19q in the region 19q13.1-q13.2. Since then, using data from a short tandem repeat-polymorphism linkage map of Chromosome 19 and recently developed microsatellite markers in this region, we have been able to further refine the localization of the Chromosome 19q CRD-causing gene. Seven new microsatellite markers were used to genotype 34 affected subjects, 22 unaffected subjects, and 15 spouses. Two-point, multipoint, and FASTMAP analyses were performed. 11 refs., 1 tab.
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genetic linkage of cone rod retinal dystrophy to Chromosome 19q and evidence for segregation distortion
Nature Genetics, 1994Co-Authors: K Evans, Cheryl Y Gregory, Alan Fryer, Josephine Duvallyoung, Chris F Inglehearn, Joanne L Whittaker, Rachel Butler, Neil D Ebenezer, David M Hunt, S S BhattacharyaAbstract:Inherited retinal dystrophies are the most common cause of childhood blindness in the developed world. Cone-rod retinal dystrophies are severe examples of this group of disorders. Analysis of a large cone-rod dystrophy pedigree suggested that inheritance within the family was influenced by meiotic drive (p = 0.008), a rare segregation distortion in human genetics. Two-point linkage analysis showed significant linkage with three markers mapping to Chromosome 19q. Multipoint analysis gave a maximum lod score of 10.08 (theta = 0.05) distal to D19S47. Cone-rod dystrophy is therefore assigned to 19q13.1-q13.2 and a new candidate locus for other retinal dystrophies is identified.
E Haberlandt - One of the best experts on this subject based on the ideXlab platform.
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split hand split foot malformation associated with sensorineural deafness inner and middle ear malformation hypodontia congenital vertical talus and deletion of eight microsatellite markers in 7q21 1 q21 3
Journal of Medical Genetics, 2001Co-Authors: E Haberlandt, Judith Loffler, Almut Hirststadlmann, Bernd Stockl, Peter Heinzerian, Werner Judmaier, Gerd Utermann, H Fischer, Thomas Müller, Richard J.h. SmithAbstract:Editor—The split hand/split foot malformation (SHFM, MIM 183600) is a central reduction defect of the hands and feet and occurs both as an isolated malformation and as part of several syndromes including the EEC syndrome (MIM 129900). We report on a 2 year old boy with SHFM associated with features of ectodermal hypoplasia, a submucous cleft palate, congenital vertical talus, malformations of the middle ear, profound sensorineural hearing loss resulting from Mondini dysplasia, and a de novo deletion of the paternal Chromosome 7q21.1-q21.3. This patient with syndromic SHFM represents a case of atypical EEC syndrome, but also displays abnormalities previously not associated with SHFM or EEC syndrome. The classical features of the autosomal dominant inherited EEC syndrome are ectrodactyly, ectodermal dysplasia, and clefting of the lip/palate. In most patients, there are additional anomalies typically affecting the urogenital and lacrimal systems.1 2 Some patients also have dysmorphic facies, a tendency to infectious disease, endocrine disorders, and mental retardation. This phenotypic variability has become increasingly apparent over the last 15 years3 4 and numerous related and overlapping syndromes have been delineated by many investigators.5 In an attempt to clarify classification, major and minor criteria for the diagnosis of EEC syndrome have been elaborated.3 4 Dominant inheritance of EEC has been documented in several large multigenerational families.6 At least 15 patients have been reported to have cytogenetic abnormalities of Chromosome 7q21.2-7q22.1, including nine patients with interstitial deletions.7-9 In addition, mutations in the gene encoding the transactivation factor p63 on Chromosome 3q27 have been identified in familial and sporadic cases of EEC syndrome.10 A third locus was mapped to Chromosome 19q,11 further delineating the genetic heterogeneity of this syndrome. The reason for the phenotypic heterogeneity in EEC syndrome patients with 7q abnormalities is unclear …
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split hand split foot malformation associated with sensorineural deafness inner and middle ear malformation hypodontia congenital vertical talus and deletion of eight microsatellite markers in 7q21 1 q21 3
Journal of Medical Genetics, 2001Co-Authors: E Haberlandt, Judith Loffler, Almut Hirststadlmann, Bernd Stockl, Peter Heinzerian, Werner Judmaier, Gerd Utermann, H Fischer, Thomas Müller, Richard J.h. SmithAbstract:Editor—The split hand/split foot malformation (SHFM, MIM 183600) is a central reduction defect of the hands and feet and occurs both as an isolated malformation and as part of several syndromes including the EEC syndrome (MIM 129900). We report on a 2 year old boy with SHFM associated with features of ectodermal hypoplasia, a submucous cleft palate, congenital vertical talus, malformations of the middle ear, profound sensorineural hearing loss resulting from Mondini dysplasia, and a de novo deletion of the paternal Chromosome 7q21.1-q21.3. This patient with syndromic SHFM represents a case of atypical EEC syndrome, but also displays abnormalities previously not associated with SHFM or EEC syndrome. The classical features of the autosomal dominant inherited EEC syndrome are ectrodactyly, ectodermal dysplasia, and clefting of the lip/palate. In most patients, there are additional anomalies typically affecting the urogenital and lacrimal systems.1 2 Some patients also have dysmorphic facies, a tendency to infectious disease, endocrine disorders, and mental retardation. This phenotypic variability has become increasingly apparent over the last 15 years3 4 and numerous related and overlapping syndromes have been delineated by many investigators.5 In an attempt to clarify classification, major and minor criteria for the diagnosis of EEC syndrome have been elaborated.3 4 Dominant inheritance of EEC has been documented in several large multigenerational families.6 At least 15 patients have been reported to have cytogenetic abnormalities of Chromosome 7q21.2-7q22.1, including nine patients with interstitial deletions.7-9 In addition, mutations in the gene encoding the transactivation factor p63 on Chromosome 3q27 have been identified in familial and sporadic cases of EEC syndrome.10 A third locus was mapped to Chromosome 19q,11 further delineating the genetic heterogeneity of this syndrome. The reason for the phenotypic heterogeneity in EEC syndrome patients with 7q abnormalities is unclear …
K Evans - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 19q cone rod retinal dystrophy ocular phenotype
Archives of Ophthalmology, 1995Co-Authors: K Evans, S S Bhattacharya, Josephine Duvallyoung, Fred W Fitzke, Geoffrey B Arden, Alan C BirdAbstract:Objective: To describe the phenotype in a family with dominantly inherited cone-rod dystrophy with Chromosome assignment to a 19q locus, and to correlate this with current classifications of this retinal dystrophy. Design: A detailed clinical examination including Goldmann perimetry was undertaken in all family members. Six members under the age of 30 years underwent dark-adapted electroretinography, color contrast-sensitivity measurement, dark-adapted static perimetry, and dark adaptometry. Patients: The study included 34 affected and 22 unaffected patients in four generations of a pedigree that manifested autosomal dominant cone-rod retinal dystrophy linked to a Chromosome 19q locus by genetic linkage analysis. Results: Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than rod function. Conclusions: The phenotype associated with this mutation does not fit well into previous subtypes of conerod dystrophy. Further studies will be needed to correlate specific genetic mutations in this group of conditions with the various clinical phenotypes.
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refinement of the cone rod retinal dystrophy locus on Chromosome 19q
American Journal of Human Genetics, 1994Co-Authors: Cheryl Y Gregory, K Evans, Joanne Whittaker, Alan Fryer, J Weissenbach, S S BhattacharyaAbstract:Cone-rod dystrophy (CRD) is a severe example of an inherited retinal dystrophy: ophthalmic diseases that as a group constitute the commonest causes of blindness in children in the developed world and account for a significant proportion of visual handicap in adults. Two case reports suggested loci for CRD-causing genes on Chromosomes 18q and Chromosome 17q. Recently, we reported the results of a total genome search that localized an autosomal dominant form of CRD to Chromosome 19q in the region 19q13.1-q13.2. Since then, using data from a short tandem repeat-polymorphism linkage map of Chromosome 19 and recently developed microsatellite markers in this region, we have been able to further refine the localization of the Chromosome 19q CRD-causing gene. Seven new microsatellite markers were used to genotype 34 affected subjects, 22 unaffected subjects, and 15 spouses. Two-point, multipoint, and FASTMAP analyses were performed. 11 refs., 1 tab.
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genetic linkage of cone rod retinal dystrophy to Chromosome 19q and evidence for segregation distortion
Nature Genetics, 1994Co-Authors: K Evans, Cheryl Y Gregory, Alan Fryer, Josephine Duvallyoung, Chris F Inglehearn, Joanne L Whittaker, Rachel Butler, Neil D Ebenezer, David M Hunt, S S BhattacharyaAbstract:Inherited retinal dystrophies are the most common cause of childhood blindness in the developed world. Cone-rod retinal dystrophies are severe examples of this group of disorders. Analysis of a large cone-rod dystrophy pedigree suggested that inheritance within the family was influenced by meiotic drive (p = 0.008), a rare segregation distortion in human genetics. Two-point linkage analysis showed significant linkage with three markers mapping to Chromosome 19q. Multipoint analysis gave a maximum lod score of 10.08 (theta = 0.05) distal to D19S47. Cone-rod dystrophy is therefore assigned to 19q13.1-q13.2 and a new candidate locus for other retinal dystrophies is identified.