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Hercília Guimarães - One of the best experts on this subject based on the ideXlab platform.
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A novel mutation in FOXF1 gene associated with Alveolar Capillary Dysplasia with misalignment of pulmonary veins, intestinal malrotation and annular pancreas.
Neonatology, 2013Co-Authors: Joana O. Miranda, Gustavo Rocha, Otília Brandão, Paulo Soares, Helder Morgado, Maria Joao Baptista, Ines Azevedo, Susana Fernandes, Partha Sen, Hercília GuimarãesAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, neonatal developmental lung disorder, which usually presents as persistent pulmonary hypertension unresponsive to treatment. The authors report the case of a neonate with persistent pulmonary hypertension, associated with duodenal stenosis secondary to annular pancreas and intestinal malrotation. Support treatment, inhaled nitric oxide, oral sildenafil and nebulized iloprost were used with no clinical improvement. The neonate presented an overwhelming course, with hypoxemia refractory to treatment. At autopsy lung histology showed the characteristic features of ACD/MPV. DNA sequence analysis revealed a heterozygous nonsense mutation c.539C>A;p.S180X, in the first exon of FOXF1. FOXF1 has been identified as one of the genes responsible for ACD/MPV associated with multiple congenital malformations. This clinical case is the first report of a heterozygous nonsense mutation c.539C>A;p.S180X in the first exon of FOXF1, in a patient with ACD/MPV associated with annular pancreas and intestinal malrotation.
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Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV): A Case Series.
Case reports in critical care, 2013Co-Authors: Joana O. Miranda, Gustavo Rocha, Henrique Soares, Ana Vilan, Otília Brandão, Hercília GuimarãesAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, developmental lung disorder, which usually presents as persistent pulmonary hypertension of the newborn (PPHN) unresponsive to treatment. The authors present their own experience with three cases admitted during the last 15 years.
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Alveolar Capillary Dysplasia with misalignment of pulmonary veins acd mpv a case series
Case reports in critical care, 2013Co-Authors: Joana O. Miranda, Gustavo Rocha, Henrique Soares, Ana Vilan, Otília Brandão, Hercília GuimarãesAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, developmental lung disorder, which usually presents as persistent pulmonary hypertension of the newborn (PPHN) unresponsive to treatment. The authors present their own experience with three cases admitted during the last 15 years.
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a novel mutation in foxf1 gene associated with Alveolar Capillary Dysplasia with misalignment of pulmonary veins intestinal malrotation and annular pancreas
Neonatology, 2013Co-Authors: Joana O. Miranda, Gustavo Rocha, Otília Brandão, Paulo Soares, Helder Morgado, Maria Joao Baptista, Ines Azevedo, Susana Fernandes, Hercília GuimarãesAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, neonatal developmental lung disorder, which usually presents as persistent pulmonary hypertension unrespon
Partha Sen - One of the best experts on this subject based on the ideXlab platform.
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Comparative Analyses of Lung Transcriptomes in Patients with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins and in Foxf1 Heterozygous Knockout Mice
2016Co-Authors: Partha Sen, Avinash V. Dharmadhikari, Tadeusz Majewski, Mahmoud A. Mohammad, Tanya V. Kalin, Joanna Zabielska, Xiaomeng Ren, Molly Bray, Hannah M. Brown, Stephen WeltyAbstract:Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a developmental disorder of the lungs, primarily affecting their vasculature. FOXF1 haploinsufficiency due to heterozygous genomic deletions and point mutations have been reported in most patients with ACDMPV. The majority of mice with heterozygous loss-of-function of Foxf1 exhibit neonatal lethality with evidence of pulmonary hemorrhage in some of them. By comparing transcriptomes of human ACDMPV lungs with control lungs using expression arrays, we found that several genes and pathways involved in lung development, angiogenesis, and in pulmonary hypertension development, were deregulated. Similar transcriptiona
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Two deletions overlapping a distant FOXF1 enhancer unravel the role of lncRNA LINC01081 in etiology of Alveolar Capillary Dysplasia with misalignment of pulmonary veins.
American Journal of Medical Genetics Part A, 2014Co-Authors: Przemyslaw Szafranski, Frances V White, Avinash V. Dharmadhikari, Jennifer A Wambach, Chris T Towe, Pirooz Eghtesady, Gail H Deutsch, R. Mark Grady, F. Sessions Cole, Partha SenAbstract:Position effects due to disruption of distant cis-regulatory regions have been reported for over 40 human gene loci; however, the underlying mechanisms of long-range gene regulation remain largely unknown. We report on two patients with Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACDMPV) caused by overlapping genomic deletions that included a distant FOXF1 transcriptional enhancer mapping 0.3 Mb upstream to FOXF1 on 16q24.1. In one patient with atypical late-onset ACDMPV, a ∼1.5 Mb deletion removed the proximal 43% of this enhancer, leaving the lung-specific long non-coding RNA (lncRNA) gene LINC01081 intact. In the second patient with severe neonatal-onset ACDMPV, an overlapping ∼194 kb deletion disrupted LINC01081. Both deletions arose de novo on maternal copy of the chromosome 16, supporting the notion that FOXF1 is paternally imprinted in the human lungs. RNAi-mediated knock-down of LINC01081 in normal fetal lung fibroblasts showed that this lncRNA positively regulates FOXF1 transcript level, further indicating that decrease in LINC01081 expression can contribute to development of ACDMPV.
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Comparative analyses of lung transcriptomes in patients with Alveolar Capillary Dysplasia with misalignment of pulmonary veins and in foxf1 heterozygous knockout mice
PloS one, 2014Co-Authors: Partha Sen, Avinash V. Dharmadhikari, Tadeusz Majewski, Mahmoud A. Mohammad, Tanya V. Kalin, Joanna Zabielska, Xiaomeng Ren, Hannah M. Brown, Molly S. Bray, Stephen E. WeltyAbstract:Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a developmental disorder of the lungs, primarily affecting their vasculature. FOXF1 haploinsufficiency due to heterozygous genomic deletions and point mutations have been reported in most patients with ACDMPV. The majority of mice with heterozygous loss-of-function of Foxf1 exhibit neonatal lethality with evidence of pulmonary hemorrhage in some of them. By comparing transcriptomes of human ACDMPV lungs with control lungs using expression arrays, we found that several genes and pathways involved in lung development, angiogenesis, and in pulmonary hypertension development, were deregulated. Similar transcriptional changes were found in lungs of the postnatal day 0.5 Foxf1+/− mice when compared to their wildtype littermate controls; 14 genes, COL15A1, COL18A1, COL6A2, ESM1, FSCN1, GRINA, IGFBP3, IL1B, MALL, NOS3, RASL11B, MATN2, PRKCDBP, and SIRPA, were found common to both ACDMPV and Foxf1 heterozygous lungs. Our results advance knowledge toward understanding of the molecular mechanism of ACDMPV, lung development, and its vasculature pathology. These data may also be useful for understanding etiologies of other lung disorders, e.g. pulmonary hypertension, bronchopulmonary Dysplasia, or cancer.
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A novel mutation in FOXF1 gene associated with Alveolar Capillary Dysplasia with misalignment of pulmonary veins, intestinal malrotation and annular pancreas.
Neonatology, 2013Co-Authors: Joana O. Miranda, Gustavo Rocha, Otília Brandão, Paulo Soares, Helder Morgado, Maria Joao Baptista, Ines Azevedo, Susana Fernandes, Partha Sen, Hercília GuimarãesAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, neonatal developmental lung disorder, which usually presents as persistent pulmonary hypertension unresponsive to treatment. The authors report the case of a neonate with persistent pulmonary hypertension, associated with duodenal stenosis secondary to annular pancreas and intestinal malrotation. Support treatment, inhaled nitric oxide, oral sildenafil and nebulized iloprost were used with no clinical improvement. The neonate presented an overwhelming course, with hypoxemia refractory to treatment. At autopsy lung histology showed the characteristic features of ACD/MPV. DNA sequence analysis revealed a heterozygous nonsense mutation c.539C>A;p.S180X, in the first exon of FOXF1. FOXF1 has been identified as one of the genes responsible for ACD/MPV associated with multiple congenital malformations. This clinical case is the first report of a heterozygous nonsense mutation c.539C>A;p.S180X in the first exon of FOXF1, in a patient with ACD/MPV associated with annular pancreas and intestinal malrotation.
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A familial case of Alveolar Capillary Dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human
European journal of human genetics : EJHG, 2012Co-Authors: Partha Sen, Claire Langston, Romana Gerychová, Petr Janku, Marta Jezova, Iveta Valášková, Colby Navarro, Iris Silva, Stephen E. Welty, John W. BelmontAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.
Claire Langston - One of the best experts on this subject based on the ideXlab platform.
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Novel FOXF1 Deep Intronic Deletion Causes Lethal Lung Developmental Disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins
Human mutation, 2013Co-Authors: Przemyslaw Szafranski, Yaping Yang, Melissa U. Nelson, Matthew J. Bizzarro, Raffaella A. Morotti, Claire Langston, Pawel StankiewiczAbstract:Haploinsufficiency of FOXF1 causes an autosomal dominant neonatally lethal lung disorder, Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACDMPV). We identified novel 0.8-kb deletion within the 1.4-kb intron of FOXF1 in a deceased newborn diagnosed with ACDMPV. The deletion arose de novo on the maternal copy of the chromosome 16, and did not affect FOXF1 minigene splicing tested in lung fibroblasts. However, FOXF1 transcript level in the ACDMPV peripheral lung tissue was reduced by almost 40%. We found that, in an in vitro reporter assay, the FOXF1 intron exhibited moderate transcriptional enhancer activity, correlating with the presence of binding sites for expression regulators CTCF and CEBPB, whereas its truncated copy, which lost major CTCF and CEBPB-binding sites, inhibited the FOXF1 promoter. Our data further emphasize the importance of testing the non-protein coding regions of the genome currently not covered by diagnostic chromosomal microarray analyses or whole-exome sequencing.
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Inversion upstream of FOXF1 in a case of lethal Alveolar Capillary Dysplasia with misalignment of pulmonary veins.
American Journal of Medical Genetics Part A, 2013Co-Authors: Toshima Z. Parris, Claire Langston, Ali Moussavi Nik, Sailesh Kotecha, Khalil Helou, Craig Platt, Peter CarlssonAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACDMPV) is a congenital malformation that leads to severe pulmonary hypertension and respiratory failure. It has been associated with deletion of, or mutation in, FOXF1 on 16q24.1, a gene encoding a forkhead transcription factor expressed in the mesenchyme of the developing lung. Here we report on the identification of a pericentric inversion on chromosome 16 (p11.2q24.1) in a case of lethal ACDMPV with atrioventricular septal defect and duodenal atresia. Array-CGH indicated that the inversion is balanced, and FISH showed that the q-arm breakpoint occurs 134 ± 10 kb upstream (5′; centromeric) of FOXF1. This is suggestive of cis-regulatory elements located more than 130 kb 5′ of FOXF1, and analysis of genome-wide data sets of chromatin modifications in two different cell types suggested that the FOXF1 regulatory domain covers more than 300 kb, and perhaps up to 433 kb, upstream of the gene, but only 3 kb downstream. The 588 kb gene-free region between FOXF1 and the next gene in the centromeric direction, IRF8, is highly conserved between species and divided into two distinct regulatory domains by an insulator element. Another putative insulator occurs just downstream of FOXF1. Our results further strengthen the association between FOXF1 and a spectrum of malformations that include ACDMPV, atrioventricular septal defects, and gastrointestinal atresia. Furthermore, the presented analysis aids in defining the critical genomic region for this syndrome.
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A familial case of Alveolar Capillary Dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human
European journal of human genetics : EJHG, 2012Co-Authors: Partha Sen, Claire Langston, Romana Gerychová, Petr Janku, Marta Jezova, Iveta Valášková, Colby Navarro, Iris Silva, Stephen E. Welty, John W. BelmontAbstract:Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.
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Expression of angiogenic and vasculogenic proteins in the lung in Alveolar Capillary Dysplasia/misalignment of pulmonary veins: An immunohistochemical study
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, 2010Co-Authors: Partha Sen, Tiyashi Choudhury, E. O'brian Smith, Claire LangstonAbstract:Abstract Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, universally fatal developmental disorder of the lung affecting both the parenchyma and the vasculature. Its cause remains incompletely understood; the occurrence of familial cases has suggested a genetic abnormality. While several candidate genes have been studied previously, the affected pathway(s) have not yet been fully defined. The expression patterns of 8 gene products (endothelial nitric oxide synthase-3, fetal liver kinase-1, hypoxia inducible factor 1α, Von Hippel Lindau protein, 3 vascular endothelial growth factors [VEGF147, VEGFC1, and VEGFA20], and activin receptor-like kinase 1), all known to have a role in vascular development in the lung, were studied in 13 ACD/MPV and 17 control lungs by immunohistochemistry to further address the underlying molecular abnormality. Expression was graded with regard to degree and extent for multiple components of the lung parenchyma and pulmonary vasculature for e...
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expression of angiogenic and vasculogenic proteins in the lung in Alveolar Capillary Dysplasia misalignment of pulmonary veins an immunohistochemical study
Pediatric and Developmental Pathology, 2010Co-Authors: Partha Sen, Tiyashi Choudhury, Obrian E Smith, Claire LangstonAbstract:Abstract Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, universally fatal developmental disorder of the lung affecting both the parenchyma and the vasculature. Its cause remains incompletely understood; the occurrence of familial cases has suggested a genetic abnormality. While several candidate genes have been studied previously, the affected pathway(s) have not yet been fully defined. The expression patterns of 8 gene products (endothelial nitric oxide synthase-3, fetal liver kinase-1, hypoxia inducible factor 1α, Von Hippel Lindau protein, 3 vascular endothelial growth factors [VEGF147, VEGFC1, and VEGFA20], and activin receptor-like kinase 1), all known to have a role in vascular development in the lung, were studied in 13 ACD/MPV and 17 control lungs by immunohistochemistry to further address the underlying molecular abnormality. Expression was graded with regard to degree and extent for multiple components of the lung parenchyma and pulmonary vasculature for e...
Simon Robinson - One of the best experts on this subject based on the ideXlab platform.
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Alveolar Capillary Dysplasia with misalignment of pulmonary veins acd mpv awareness prevents extended or futile ecmo use
Indian Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Ullas Angadi, Vishnuvardhan Meedimale, Simon RobinsonAbstract:Background Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, congenital lung disorder involving abnormal development of the Capillary vascular system around the alveoli of the lungs, which clinically presents as persistent pulmonary hypertension of the newborn (PPHN) refractory to treatment. It has been linked to the gene FOXF1 on chromosome 16q24.1–q24.2. Histopathological examination by lung biopsy is the gold standard for diagnosis.
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Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV)—awareness prevents extended or futile ECMO use
Indian Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Ullas Angadi, Vishnuvardhan Meedimale, Simon RobinsonAbstract:Background Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, congenital lung disorder involving abnormal development of the Capillary vascular system around the alveoli of the lungs, which clinically presents as persistent pulmonary hypertension of the newborn (PPHN) refractory to treatment. It has been linked to the gene FOXF1 on chromosome 16q24.1–q24.2. Histopathological examination by lung biopsy is the gold standard for diagnosis.
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Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV)—awareness prevents extended or futile ECMO use
Indian Journal of Thoracic and Cardiovascular Surgery, 2014Co-Authors: Ullas Angadi, Vishnuvardhan Meedimale, Simon RobinsonAbstract:Background Alveolar Capillary Dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, congenital lung disorder involving abnormal development of the Capillary vascular system around the alveoli of the lungs, which clinically presents as persistent pulmonary hypertension of the newborn (PPHN) refractory to treatment. It has been linked to the gene FOXF1 on chromosome 16q24.1–q24.2. Histopathological examination by lung biopsy is the gold standard for diagnosis. Materials and methods We present four cases of ACD/MPV who were referred for ECMO support with a diagnosis of PPHN with no apparent congenital anomalies. Results All the newborns had an overwhelming course, with PPHN and hypoxemia refractory to treatment. The diagnosis of ACD/MPV was established by ante-mortem lung biopsy in all cases. Intensive care treatment was withdrawn post diagnosis, with none of the four surviving. Conclusions Early lung biopsy for a histological diagnosis allows expensive and ineffective treatment to be avoided. Lung biopsy can be performed with low risk and high-diagnostic yield for Alveolar Capillary Dysplasia.
M J Del Cerro - One of the best experts on this subject based on the ideXlab platform.
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Alveolar Capillary Dysplasia with misalignment of the pulmonary veins associated with aortic coarctation and intestinal malrotation
Journal of Perinatology, 2014Co-Authors: A Avilaalvarez, L R Schteffer, Lucia Deiros, F Santos, M J Del CerroAbstract:Alveolar Capillary Dysplasia with misalignment of the pulmonary veins associated with aortic coarctation and intestinal malrotation
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Alveolar Capillary Dysplasia with misalignment of the pulmonary veins associated with aortic coarctation and intestinal malrotation
Journal of Perinatology, 2014Co-Authors: V Arreo Del Val, L R Schteffer, Lucia Deiros, F Santos, A Avila-alvarez, M J Del CerroAbstract:Alveolar Capillary Dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare and lethal cause of refractory pulmonary hypertension of the newborn. We describe the clinical course of a neonate with refractory pulmonary hypertension diagnosed with ACD/MPV, aortic coarctation and other not previously reported associated malformations.