The Experts below are selected from a list of 34683 Experts worldwide ranked by ideXlab platform
Errol C. Friedberg - One of the best experts on this subject based on the ideXlab platform.
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a novel xpc pathogenic variant detected in Archival Material from a patient diagnosed with xeroderma pigmentosum a case report and review of the genetic variants reported in xpc
DNA Repair, 2007Co-Authors: Amanda Riverabegeman, Lisa D. Mcdaniel, Roger A. Schultz, Errol C. FriedbergAbstract:The disease Xeroderma Pigmentosum (XP) is genetically heterogeneous and defined by pathogenic variants (formerly termed mutations) in any of eight different genes. Pathogenic variants in the XPC gene are the most commonly observed in US patients. Moreover, pathogenic variants in just four of the genes, XPA, XPC, XPD/ERCC2 and XPV/POLH account for 91% of all XP cases worldwide. In the current study, we describe the clinical, histopathologic, molecular genetic, and pathophysiological features of a 19-year-old female patient clinically diagnosed with XP as an infant. Analysis of Archival Material reveals a novel variation of a 13 base pair deletion in XPC exon 14 and a previously reported A>C missense pathogenic variant in the proximal splice site for XPC exon 6. Both variations induce frameshifts most likely leading to a truncated XPC protein product. Quantitative RT-PCR also revealed reduced mRNA levels in the archived specimen. Analysis of the XPA, XPD/ERCC2 and XPV/POLH genes in the current specimen failed to reveal pathologic variants. All previously reported pathogenic variants, polymorphisms and known amino acid changes for the XPC gene are compiled and described in the current nomenclature. Given the relative ease of screening for genetic variation and the potential role for such variation in human disease, a proposal for screening appropriate Archival Materials for alterations in the four most prevalent XP genes is presented.
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Validation of XP-C pathogenic variations in Archival Material from a live XP patient.
DNA repair, 2006Co-Authors: Lisa D. Mcdaniel, Amanda Rivera-begeman, Ana T.b. Doughty, Roger A. Schultz, Errol C. FriedbergAbstract:Xeroderma pigmentosum (XP) genetic complementation group C (XP-C) is the most common form of the disease worldwide. Thirty-four distinct genetic defects have been identified in 45 XP-C patients. Further identification of such defects and the frequency of their occurrence offers the potential of generating diagnostic and prognostic molecular screening panels. Archival Material (such as formalin-fixed paraffin embedded skin) may be useful for the identification of novel genetic variations and for documenting the frequency of individual genetic defects in patients who are no longer available for study. However, the use of Archival Material precludes direct analysis of changes in the mRNA resulting from genomic changes. The serendipitous reacquisition of an XP individual in whom genetic defects were previously characterized in Archival Material allowed confirmation of the defects as well as a direct analysis of the consequences of these defects on mRNA, mRNA expression and on cellular phenotypes.
Lisa D. Mcdaniel - One of the best experts on this subject based on the ideXlab platform.
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a novel xpc pathogenic variant detected in Archival Material from a patient diagnosed with xeroderma pigmentosum a case report and review of the genetic variants reported in xpc
DNA Repair, 2007Co-Authors: Amanda Riverabegeman, Lisa D. Mcdaniel, Roger A. Schultz, Errol C. FriedbergAbstract:The disease Xeroderma Pigmentosum (XP) is genetically heterogeneous and defined by pathogenic variants (formerly termed mutations) in any of eight different genes. Pathogenic variants in the XPC gene are the most commonly observed in US patients. Moreover, pathogenic variants in just four of the genes, XPA, XPC, XPD/ERCC2 and XPV/POLH account for 91% of all XP cases worldwide. In the current study, we describe the clinical, histopathologic, molecular genetic, and pathophysiological features of a 19-year-old female patient clinically diagnosed with XP as an infant. Analysis of Archival Material reveals a novel variation of a 13 base pair deletion in XPC exon 14 and a previously reported A>C missense pathogenic variant in the proximal splice site for XPC exon 6. Both variations induce frameshifts most likely leading to a truncated XPC protein product. Quantitative RT-PCR also revealed reduced mRNA levels in the archived specimen. Analysis of the XPA, XPD/ERCC2 and XPV/POLH genes in the current specimen failed to reveal pathologic variants. All previously reported pathogenic variants, polymorphisms and known amino acid changes for the XPC gene are compiled and described in the current nomenclature. Given the relative ease of screening for genetic variation and the potential role for such variation in human disease, a proposal for screening appropriate Archival Materials for alterations in the four most prevalent XP genes is presented.
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Validation of XP-C pathogenic variations in Archival Material from a live XP patient.
DNA repair, 2006Co-Authors: Lisa D. Mcdaniel, Amanda Rivera-begeman, Ana T.b. Doughty, Roger A. Schultz, Errol C. FriedbergAbstract:Xeroderma pigmentosum (XP) genetic complementation group C (XP-C) is the most common form of the disease worldwide. Thirty-four distinct genetic defects have been identified in 45 XP-C patients. Further identification of such defects and the frequency of their occurrence offers the potential of generating diagnostic and prognostic molecular screening panels. Archival Material (such as formalin-fixed paraffin embedded skin) may be useful for the identification of novel genetic variations and for documenting the frequency of individual genetic defects in patients who are no longer available for study. However, the use of Archival Material precludes direct analysis of changes in the mRNA resulting from genomic changes. The serendipitous reacquisition of an XP individual in whom genetic defects were previously characterized in Archival Material allowed confirmation of the defects as well as a direct analysis of the consequences of these defects on mRNA, mRNA expression and on cellular phenotypes.
Roger A. Schultz - One of the best experts on this subject based on the ideXlab platform.
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a novel xpc pathogenic variant detected in Archival Material from a patient diagnosed with xeroderma pigmentosum a case report and review of the genetic variants reported in xpc
DNA Repair, 2007Co-Authors: Amanda Riverabegeman, Lisa D. Mcdaniel, Roger A. Schultz, Errol C. FriedbergAbstract:The disease Xeroderma Pigmentosum (XP) is genetically heterogeneous and defined by pathogenic variants (formerly termed mutations) in any of eight different genes. Pathogenic variants in the XPC gene are the most commonly observed in US patients. Moreover, pathogenic variants in just four of the genes, XPA, XPC, XPD/ERCC2 and XPV/POLH account for 91% of all XP cases worldwide. In the current study, we describe the clinical, histopathologic, molecular genetic, and pathophysiological features of a 19-year-old female patient clinically diagnosed with XP as an infant. Analysis of Archival Material reveals a novel variation of a 13 base pair deletion in XPC exon 14 and a previously reported A>C missense pathogenic variant in the proximal splice site for XPC exon 6. Both variations induce frameshifts most likely leading to a truncated XPC protein product. Quantitative RT-PCR also revealed reduced mRNA levels in the archived specimen. Analysis of the XPA, XPD/ERCC2 and XPV/POLH genes in the current specimen failed to reveal pathologic variants. All previously reported pathogenic variants, polymorphisms and known amino acid changes for the XPC gene are compiled and described in the current nomenclature. Given the relative ease of screening for genetic variation and the potential role for such variation in human disease, a proposal for screening appropriate Archival Materials for alterations in the four most prevalent XP genes is presented.
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Validation of XP-C pathogenic variations in Archival Material from a live XP patient.
DNA repair, 2006Co-Authors: Lisa D. Mcdaniel, Amanda Rivera-begeman, Ana T.b. Doughty, Roger A. Schultz, Errol C. FriedbergAbstract:Xeroderma pigmentosum (XP) genetic complementation group C (XP-C) is the most common form of the disease worldwide. Thirty-four distinct genetic defects have been identified in 45 XP-C patients. Further identification of such defects and the frequency of their occurrence offers the potential of generating diagnostic and prognostic molecular screening panels. Archival Material (such as formalin-fixed paraffin embedded skin) may be useful for the identification of novel genetic variations and for documenting the frequency of individual genetic defects in patients who are no longer available for study. However, the use of Archival Material precludes direct analysis of changes in the mRNA resulting from genomic changes. The serendipitous reacquisition of an XP individual in whom genetic defects were previously characterized in Archival Material allowed confirmation of the defects as well as a direct analysis of the consequences of these defects on mRNA, mRNA expression and on cellular phenotypes.
Cristina R. Antonescu - One of the best experts on this subject based on the ideXlab platform.
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RBM10-TFE3 Renal Cell Carcinoma: A Potential Diagnostic Pitfall Due to Cryptic Intrachromosomal Xp11.2 Inversion Resulting in False-negative TFE3 FISH.
The American journal of surgical pathology, 2017Co-Authors: Pedram Argani, Lei Zhang, Victor E. Reuter, Satish K. Tickoo, Cristina R. AntonescuAbstract:Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in Archival Material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion. TFE3 rearrangement was not detected by conventional TFE3 break-apart FISH, but was suggested by strong diffuse TFE3 immunoreactivity in a clean background. We then developed novel fosmid probes to detect the RBM10-TFE3 gene fusion in Archival Material. These cases validate RBM10-TFE3 as a recurrent gene fusion in Xp11 translocation RCC, illustrate a source of false-negative TFE3 break-apart FISH, and highlight the complementary role of TFE3 IHC and TFE3 FISH.
Amanda Riverabegeman - One of the best experts on this subject based on the ideXlab platform.
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a novel xpc pathogenic variant detected in Archival Material from a patient diagnosed with xeroderma pigmentosum a case report and review of the genetic variants reported in xpc
DNA Repair, 2007Co-Authors: Amanda Riverabegeman, Lisa D. Mcdaniel, Roger A. Schultz, Errol C. FriedbergAbstract:The disease Xeroderma Pigmentosum (XP) is genetically heterogeneous and defined by pathogenic variants (formerly termed mutations) in any of eight different genes. Pathogenic variants in the XPC gene are the most commonly observed in US patients. Moreover, pathogenic variants in just four of the genes, XPA, XPC, XPD/ERCC2 and XPV/POLH account for 91% of all XP cases worldwide. In the current study, we describe the clinical, histopathologic, molecular genetic, and pathophysiological features of a 19-year-old female patient clinically diagnosed with XP as an infant. Analysis of Archival Material reveals a novel variation of a 13 base pair deletion in XPC exon 14 and a previously reported A>C missense pathogenic variant in the proximal splice site for XPC exon 6. Both variations induce frameshifts most likely leading to a truncated XPC protein product. Quantitative RT-PCR also revealed reduced mRNA levels in the archived specimen. Analysis of the XPA, XPD/ERCC2 and XPV/POLH genes in the current specimen failed to reveal pathologic variants. All previously reported pathogenic variants, polymorphisms and known amino acid changes for the XPC gene are compiled and described in the current nomenclature. Given the relative ease of screening for genetic variation and the potential role for such variation in human disease, a proposal for screening appropriate Archival Materials for alterations in the four most prevalent XP genes is presented.