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Juha Kere - One of the best experts on this subject based on the ideXlab platform.
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Split hand/split foot malformation, deafness, and mental retardation with a complex cytogenetic rearrangement involving 7q21.3.
Journal of medical genetics, 1996Co-Authors: Jaakko Ignatius, Stephen W. Scherer, Sakari Knuutila, Barbara J. Trask, Juha KereAbstract:Split hand/split foot malformation (SHSF) has been described in several patients associated with cytogenetically visible rearrangements involving Chromosome 7q. Characterisation of these patients has led to localisation of an autosomal dominant form of SHSF to 7q21-22; the locus has been designated SHFM1. We describe a patient with a complex, apparently balanced cytogenetic rearrangement, including a translocation breakpoint at 7q21.3 near the DSS1 gene. In addition to ectrodactyly of all four limbs, the patient has congenital deafness, submucous cleft palate, microcephaly, and mental retardation. This patient represents an additional case of syndromic ectrodactyly related to the SHFM1 gene region, which may be responsible for both syndromic and non-syndromic ectrodactyly.
Kian Behbakht - One of the best experts on this subject based on the ideXlab platform.
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allelotype analysis of uterine leiomyoma localization of a potential tumor suppressor gene to a 4 cm region of Chromosome 7q
Molecular Carcinogenesis, 1998Co-Authors: O Van Der Heijden, H C Chiu, T C Park, H Takahashi, Virginia A Livolsi, J I Risinger, J C Barrett, Andrew Berchuck, A C Evans, Kian BehbakhtAbstract:Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 Chromosome arms. In general, LOH was very rare except on Chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tumor suppressor gene involved in the etiology of this tumor.
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Allelotype analysis of uterine leiomyoma: Localization of a potential tumor suppressor gene to a 4‐cM region of Chromosome 7q
Molecular carcinogenesis, 1998Co-Authors: O Van Der Heijden, H C Chiu, T C Park, H Takahashi, Virginia A Livolsi, J I Risinger, J C Barrett, Andrew Berchuck, A C Evans, Kian BehbakhtAbstract:Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 Chromosome arms. In general, LOH was very rare except on Chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tumor suppressor gene involved in the etiology of this tumor. Mol. Carcinog. 23:243–247, 1998. © 1998 Wiley-Liss, Inc.
Stephen W. Scherer - One of the best experts on this subject based on the ideXlab platform.
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Molecular Characterization of Distinct Hot Spot Regions on Chromosome 7q in Myeloid Leukemias.
Blood, 2006Co-Authors: Konstanze Döhner, Stephen W. Scherer, Marianne Habdank, Frank G. Rücker, Simone Miller, Stefan Fröhling, Lars Bullinger, Hartmut DöhnerAbstract:In recent years several groups initiated the molecular characterization of deletion and translocation breakpoints affecting the long arm of Chromosome 7 (7q−) to identify genes that are involved in the pathogenesis of myeloid leukemias. Based on these studies a commonly deleted segment (CDS) of approximately 2 Mb in size was identified in chromosomal band 7q22 flanked by the microsatellite markers D7S1503 and D7S1841. Recently, the MLL5 gene (mixed lineage leukemia 5) has been cloned and mapped to the CDS as an interesting candidate gene for Chromosome 7q associated leukemias. However, the pathogenic role of MLL5 in myeloid leukemias has not been demonstrated yet. In addition, for the less frequent deletion/translocation breakpoints affecting the distal part of Chromosome 7q a 4 to 5 Mb sized CDS was defined encompassing chromosomal bands 7q35 to q36. The heterogeneity of deletion/translocation breakpoints on 7q suggests the existence of more than one disease-related gene. We aimed to identify and characterize translocation and deletion breakpoints in a large series of myeloid leukemias with Chromosome 7q aberrations using fluorescence in situ hybridisation (FISH) and array-based comparative genomic hybridization (array CGH). Once, novel hot spot regions were identified, transcriptional map(s) were constructed allowing the identification of candidate genes, expressed sequences or miR-sites. FISH with a physical map of well defined YAC/BAC/PAC clones covering the long arm of Chromosome 7 was performed on a series of 105 myeloid leukemias [acute myeloid leukaemia, (AML); myelodysplastic syndrome (MDS); myeloproliferative disorders, (MPD)] exhibiting Chromosome 7q aberrations on banding analysis. Selected patients were analysed by array CGH and results were confirmed by hybridisation of the corresponding DNA clones. Transcriptional map(s) were constructed using public databases. While most of the deletions were large encompassing the previously published CDS, we identified a distinct 2 Mb sized CDS in the proximal part of 7q22 that was defined by five patients all exhibiting small deletions. This segment contains several candidate genes including the putative tumor-suppressor genes CUTL1, RASA4, EPO and FBXL13. Interestingly, this CDS is located close to multiple miR-sites, which usually indicate common fragile sites in the human genome. In chromosomal bands 7q35–q36 we localized the breakpoint of an unbalanced translocation from a patient with secondary AML between the markers D7S1925 and D7S1395. This region was recently characterized as a common fragile site in the human genome, named FRA7I. Furthermore, the translocation breakpoint t(3;7)(p13;q35) of a second patient with therapy-related AML was cloned into a 100 kb sized genomic segment located centromeric the CNTNAP2-gene close to the proximal border of the CDS. Our data further indicate the remarkable heterogeneity of deletion and translocation breakpoints on 7q supporting the hypothesis of multiple genes involved in 7q-associated myeloid leukemias. Using techniques such as FISH and array CGH known CDS as well as novel hot spot regions were identified. Transcriptional maps from those regions may serve as important starting points for the identification of pathogenetically relevant genes.
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Williams-Beuren Syndrome Diagnosis Using Fluorescence In Situ Hybridization
Methods in molecular medicine, 2006Co-Authors: Lucy R. Osborne, Ann M. Joseph-george, Stephen W. SchererAbstract:Williams-Beuren syndrome (WBS) is most commonly caused by a 1.5-Mb hemizygous deletion of Chromosome 7q 11.23. Other genomic rearrangements of this region have also been described, some as polymorphisms and others as rare variants, the latter often being directly associated with clinical symptoms. Fluorescence in situ hybridization of either metaphase or interphase nuclei can be used to detect all of these chromosomal rearrangements, providing the ability to test this segment of Chromosome 7 in families with a suspected diagnosis of WBS.
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Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through Chromosome 7q translocations.
Oncogene, 1999Co-Authors: Martin Corcoran, Stephen W. Scherer, Sarah Mould, Jenny A. Orchard, Rachel E. Ibbotson, R. Chapman, Andrew P. Boright, Platt C, Lap-chee Tsui, David OscierAbstract:The increased or inappropriate expression of genes with oncogenic properties through specific Chromosome translocations is an important event in the pathogenesis of B-cell lymphoproliferative diseases. Recent studies have found deletions or translocations of Chromosome 7q to be the most common cytogenetic abnormality observed in SLVL, a leukemic variant of SMZL, with the q21 – q22 region being most frequently affected. In three patients with translocations between Chromosomes 2 and 7, the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3.6 kb upstream of the transcription start site of cyclin dependent kinase 6 (CDK6). In each case the translocation event was consistent with aberrant VJ recombination between the immunoglobulin light chain region (Ig kappa) on Chromosome 2p12 and DNA sequences at 7q21, resembling the heptamer recombination site. The t(7;21) breakpoint in an additional patient with splenic marginal zone lymphoma (SMZL), resided 66 kb telomeric to the t(2;7) breakpoints juxtaposing CDK6 to an uncharacterized transcript. In two of the SLVL patient samples, the CDK6 protein was found to be markedly over expressed. These results suggest that dysregulation of CDK6 gene expression contributes to the pathogenesis of SLVL and SMZL.
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Split hand/split foot malformation, deafness, and mental retardation with a complex cytogenetic rearrangement involving 7q21.3.
Journal of medical genetics, 1996Co-Authors: Jaakko Ignatius, Stephen W. Scherer, Sakari Knuutila, Barbara J. Trask, Juha KereAbstract:Split hand/split foot malformation (SHSF) has been described in several patients associated with cytogenetically visible rearrangements involving Chromosome 7q. Characterisation of these patients has led to localisation of an autosomal dominant form of SHSF to 7q21-22; the locus has been designated SHFM1. We describe a patient with a complex, apparently balanced cytogenetic rearrangement, including a translocation breakpoint at 7q21.3 near the DSS1 gene. In addition to ectrodactyly of all four limbs, the patient has congenital deafness, submucous cleft palate, microcephaly, and mental retardation. This patient represents an additional case of syndromic ectrodactyly related to the SHFM1 gene region, which may be responsible for both syndromic and non-syndromic ectrodactyly.
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Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human Chromosome 7q
Genomics, 1996Co-Authors: Stephen W. Scherer, Robert M. Duvoisin, Rainer Kuhn, Henry H.q. Heng, Elena Belloni, Lap-chee TsuiAbstract:Metabotropic glutamate receptors (GRMs) are neurotransmitter receptors that respond to glutamate stimulations by activating GTP-binding proteins and modulating second-messsenger cascades. Eight related GRMs have been identified to date. In this study, we have mappedGRM3andGRM8to human Chromosome 7q21.1–q21.2 and 7q31.3–q32.1, respectively, using somatic cell hybrid and fluorescencein situhybridization analysis. A yeast artificial Chromosome contig was constructed surrrounding the genes, allowing their location to be integrated into the genetic and physical map of Chromosome 7.
Jaakko Ignatius - One of the best experts on this subject based on the ideXlab platform.
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Split hand/split foot malformation, deafness, and mental retardation with a complex cytogenetic rearrangement involving 7q21.3.
Journal of medical genetics, 1996Co-Authors: Jaakko Ignatius, Stephen W. Scherer, Sakari Knuutila, Barbara J. Trask, Juha KereAbstract:Split hand/split foot malformation (SHSF) has been described in several patients associated with cytogenetically visible rearrangements involving Chromosome 7q. Characterisation of these patients has led to localisation of an autosomal dominant form of SHSF to 7q21-22; the locus has been designated SHFM1. We describe a patient with a complex, apparently balanced cytogenetic rearrangement, including a translocation breakpoint at 7q21.3 near the DSS1 gene. In addition to ectrodactyly of all four limbs, the patient has congenital deafness, submucous cleft palate, microcephaly, and mental retardation. This patient represents an additional case of syndromic ectrodactyly related to the SHFM1 gene region, which may be responsible for both syndromic and non-syndromic ectrodactyly.
F. Rieger - One of the best experts on this subject based on the ideXlab platform.
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Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human Chromosome 7q: possible components of a 'chain-reaction' triggered by infectious agents in multiple sclerosis?
Journal of neurovirology, 2000Co-Authors: Hervé Perron, F. RiegerAbstract:Different groups have observed retrovirus particle (RVP) production in cell cultures from patients with multiple sclerosis (MS). This in vitro production appeared relatively specific for MS versus healthy controls, but was likely to be enhanced or activated by infectious triggers such as Herpesviruses (e.g. HSV, EBV). Independent molecular analysis of retroviral RNA associated with RVP revealed two different genetic families of endogenous retroviral elements (HERV): MSRV/HERV-W and RGH/HERV-H. Interestingly, these sequences were detected by mutually exclusive primers in RT ‐ PCR amplifications. Surprisingly, these two HERV families both contain an ancestral proviral copy inserted in Chromosome 7q21-22 region at about 1 kb of distance of each other. Another HERV-W proviral sequence is located within a T-cell alpha-delta receptor (TCR) gene in Chromosome 14q11.2 region. Interestingly, these two regions correspond to genetic loci previously identified as potentially associated with ‘multigenic’ susceptibility to MS and TCR alpha chain genetic determinants have been reported to be statistically associated with MS. A plausible role for infectious agents triggering a co-activation of the Chromosome 7q HERV tandem (replicative retrovirus and/or other virus and/or intracellular bacteria) and, eventually, other HERV copies, is discussed. The role of particular HERV polymorphism and the production of pathogenic molecules (gliotoxin and superantigen) possibly associated with retroviral expression are also evoked. An integrative concept of pathogenic ‘chain-reaction’ in MS involving several step-specific pathogenic ‘agents’ and ‘products’ somewhat interacting with particular genetic elements would federate most partial data obtained on MS, including retroviral expression. Journal of NeuroVirology (2000) 6, S67 ‐ S75.