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Oleg A Shchelochkov - One of the best experts on this subject based on the ideXlab platform.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation. © 2011 Wiley-Liss, Inc.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation.
Manjunath Nimmakayalu - One of the best experts on this subject based on the ideXlab platform.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation. © 2011 Wiley-Liss, Inc.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation.
Vincent M. Christoffels - One of the best experts on this subject based on the ideXlab platform.
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TBX2 and tbx3 act downstream of shh to maintain canonical wnt signaling during branching morphogenesis of the murine lung
Developmental Cell, 2016Co-Authors: Timo H W Ludtke, Annacarina Weiss, Vincent M. Christoffels, Irina Wojahn, Marcjens Kleppa, Jennifer Kurz, Anne M Moon, Andreas KispertAbstract:Numerous signals drive the proliferative expansion of the distal endoderm and the underlying mesenchyme during lung branching morphogenesis, but little is known about how these signals are integrated. Here, we show by analysis of conditional double mutants that the two T-box transcription factor genes TBX2 and Tbx3 act together in the lung mesenchyme to maintain branching morphogenesis. Expression of both genes depends on epithelially derived Shh signaling, with additional modulation by Bmp, Wnt, and Tgfβ signaling. Genetic rescue experiments reveal that TBX2 and Tbx3 function downstream of Shh to maintain pro-proliferative mesenchymal Wnt signaling, in part by direct repression of the Wnt antagonists Frzb and Shisa3. In combination with our previous finding that TBX2 and Tbx3 repress the cell-cycle inhibitors Cdkn1a and Cdkn1b, we conclude that TBX2 and Tbx3 maintain proliferation of the lung mesenchyme by way of at least two molecular mechanisms: regulating cell-cycle regulation and integrating the activity of multiple signaling pathways.
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Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus
Early human development, 2016Co-Authors: Nicole B. Burger, Peter J. Scambler, Vincent M. Christoffels, Monique C. Haak, Christianne J.m. De Groot, Evelien Kok, Weinian Shou, Youngsook Lee, Eunjin Cho, Mireille N. BekkerAbstract:Abstract Background In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac function or are caused by local morphological alterations in the ductus venosus. Aim The aim of this study was to investigate if the observed increased nuchal translucency, cardiac defects and abnormal lymphatic development in the examined mouse models are associated with local changes in ductus venosus morphology. Study design Mouse embryos with anomalous lymphatic development and nuchal edema ( Ccbe1 −/− embryos), mouse embryos with cardiac defects and nuchal edema ( Fkbp12 −/− , Tbx1 −/− , Chd7 fl / fl ;Mesp1Cre , Jarid2 −/− NE+ embryos) and mouse embryos with cardiac defects without nuchal edema ( TBX2 −/− , Fgf10 −/− , Jarid2 −/− NE − embryos) were examined. Embryos were analyzed from embryonic day (E) 11.5 to 15.5 using markers for endothelium, smooth muscle actin, nerve tissue and elastic fibers. Results All mutant and wild-type mouse embryos showed similar, positive endothelial and smooth muscle cell expression in the ductus venosus at E11.5–15.5. Nerve marker and elastic fiber expression were not identified in the ductus venosus in all investigated mutant and wild-type embryos. Local morphology and expression of the used markers were similar in the ductus venosus in all examined mutant and wild-type embryos. Conclusions Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. Ductus venosus flow velocity waveforms most probably reflect intracardiac pressure.
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TBX2 is expressed in the proepicardium and epicardium.
2016Co-Authors: Franziska Greulich, Carsten Rudat, Vincent M. Christoffels, Henner F. Farin, Andreas KispertAbstract:(A) Epifluorescence of a TBX2cre/+;R26mTmG/+ embryo at E9.5 reveals the contribution of formerly TBX2-expressing cells to the atrio-ventricular canal (AVC), the otic vesicle (OV), the eye (E) and the proepicardium (PE) (n = 5). The scale bar is 500 μm. (B) Lineage tracing of TBX2-expressing cells on sections of E9.5 embryos by immunofluorescent detection of a GFP reporter and/or the epicardial markers TBX18 and WT1 (left row) confirms the contribution of TBX2-expressing cells to the proepicardium (n = 3). Double immunofluorescence against GFP and TBX2 or TBX3, respectively, (right row) shows expression of TBX2 in the caudal part of the proepicardium. Note that the anti-TBX2 antibody recognizes cells that do not recombine after cre expression from the TBX2 promoter. The third picture of the lower row shows an in silico overlay of the expression domains of TBX2 and TBX3 co-stained with the TBX2-lineage label GFP on neighboring sections. Only TBX2-positive (red), TBX3-negative and GFP-positive (blue) domains relate to TBX2 expression domains (white arrowhead). The scale bars are 50 μm. (C) TBX2 but not TBX3 protein was detected by immunofluorescence against TBX2 and TBX3 in epicardial and subepicardial cells of Tbx18cre/+;R26mTmG/+ embryos at E13.5 (white arrows, n = 2). Co-staining against the Tbx18-lineage label GFP clearly identifies epicardial and epicardium-derived cells. The scale bars are 50 μm. CA, common atrium; Epi, epicardium; RV, right ventricle; SV, sinus venosus.
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T-box gene expression during epicardial development.
2016Co-Authors: Franziska Greulich, Carsten Rudat, Vincent M. Christoffels, Henner F. Farin, Andreas KispertAbstract:(A) Qualitative RT-PCR analysis detects expression of Tbx18, Tbx5, TBX20 and TBX2 but not of Tbx3 and Tbx1 in undifferentiated epicardial cells from cardiac explant cultures (Epi). 32 epicardial explant cultures were pooled and used for qualitative PCR. H2O refers to a negative control without cDNA, pos to a positive control of a tissue with known expression (see S1 Table). (B) In situ hybridization analysis of Tbx18, Tbx5, TBX20, TBX2, Tbx3 and Tbx1 expression on sagital (E9.5) and transverse (E10.5, E12.5, E14.5) sections through the heart. Shown are higher magnifications of the proepicardium (E9.5) and of the right ventricle (E10.5 to E14.5). Black arrows indicate proepicardial and epicardial expression of Tbx18, Tbx5, TBX20 and TBX2, asterisks point to known expression domains of Tbx5 and TBX20 in the atrium, and of TBX2 and Tbx3 in the liver primordium at E9.5. Black arrowheads indicate coronary artery expression of TBX2 at E14.5. Scale bars are 50 μm. CA, common atrium; CAr, coronary artery; Epi, epicardium; PE, proepicardium; RV, right ventricle; SV, sinus venosus.
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inhibition of sox2 dependent activation of shh in the ventral diencephalon by tbx3 is required for formation of the neurohypophysis
Development, 2013Co-Authors: Mark-oliver Trowe, Annacarina Weiss, Douglas J Epstein, Vincent M. Christoffels, Li Zhao, Andreas KispertAbstract:TBX2 and Tbx3 are two highly related members of the T-box transcription factor gene family that regulate patterning and differentiation of a number of tissue rudiments in the mouse. Both genes are partially co-expressed in the ventral diencephalon and the infundibulum; however, a functional requirement in murine pituitary development has not been reported. Here, we show by genetic lineage tracing that TBX2+ cells constitute the precursor population of the neurohypophysis. However, TBX2 is dispensable for neurohypophysis development as revealed by normal formation of this organ in TBX2 -deficient mice. By contrast, loss of Tbx3 from the ventral diencephalon results in a failure to establish the TBX2+ domain in this region, and a lack of evagination of the infundibulum and formation of the neurohypophysis. Rathke's pouch is severely hypoplastic, exhibits defects in dorsoventral patterning, and degenerates after E12.5. In Tbx3 -deficient embryos, the ventral diencephalon is hyperproliferative and displays an abnormal cellular architecture, probably resulting from a failure to repress transcription of Shh . We further show that Tbx3 and TBX2 repress Shh by sequestering the SRY box-containing transcription factor Sox2 away from a Shh forebrain enhancer ( SBE2 ), thus preventing its activation. These data suggest that Tbx3 is required in the ventral diencephalon to establish a Shh− domain to allow formation of the infundibulum.
Donald H Solomon - One of the best experts on this subject based on the ideXlab platform.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation. © 2011 Wiley-Liss, Inc.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation.
Heather Major - One of the best experts on this subject based on the ideXlab platform.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation. © 2011 Wiley-Liss, Inc.
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microdeletion of 17q22q23 2 encompassing TBX2 and tbx4 in a patient with congenital microcephaly thyroid duct cyst sensorineural hearing loss and pulmonary hypertension
American Journal of Medical Genetics Part A, 2011Co-Authors: Manjunath Nimmakayalu, Heather Major, Val C Sheffield, Donald H Solomon, Richard J H Smith, Shivanand R Patil, Oleg A ShchelochkovAbstract:Microdeletions of the long arm of chromosome 17 are being reported with increasing frequency. Deletions of 17q22q23.2 may represent a genetically recognizable phenotype although its spectrum of genomic abnormalities, clinical manifestations, and critical regions are not fully delineated. Isolated reports and small case series suggest that deletions of 17q22q23.2 result in haploinsufficiency of dosage sensitive genes NOG, TBX2, and TBX4, which may be responsible for many aspects of the phenotype. Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay. We describe a female patient who presented with severe congenital microcephaly, thyroglossal duct cyst, sensorineural hearing loss, mild tracheomalacia, abnormal auricles, pulmonary hypertension, developmental delay, and postnatal onset growth delay. She had no TEF/EA or heart defects. Using a high density oligonucleotide microarray, we identified a microdeletion at 17q22q23.2, resulting in the heterozygous loss of several genes, including TBX2 and TBX4 but not NOG. The breakpoints did not lie within known segmental duplications. This case helps to further delineate the critical region for TEF/EA, which is likely confined to the chromosomal region proximal to 17q23.1, and suggests that genes in 17q23.1q23.2 may be associated with thyroglossal duct cysts. The role of TBX2 and TBX4 in pulmonary hypertension warrants investigation.
