28 results on '"Anne, Moreau de Bellaing"'
Search Results
2. Common deletion variants causing protocadherin-α deficiency contribute to the complex genetics of BAV and left-sided congenital heart disease
- Author
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Polakit Teekakirikul, Wenjuan Zhu, George C. Gabriel, Cullen B. Young, Kylia Williams, Lisa J. Martin, Jennifer C. Hill, Tara Richards, Marie Billaud, Julie A. Phillippi, Jianbin Wang, Yijen Wu, Tuantuan Tan, William Devine, Jiuann-huey Lin, Abha S. Bais, Jonathan Klonowski, Anne Moreau de Bellaing, Ankur Saini, Michael X. Wang, Leonid Emerel, Nathan Salamacha, Samuel K. Wyman, Carrie Lee, Hung Sing Li, Anastasia Miron, Jingyu Zhang, Jianhua Xing, Dennis M. McNamara, Erik Fung, Paul Kirshbom, William Mahle, Lazaros K. Kochilas, Yihua He, Vidu Garg, Peter White, Kim L. McBride, D. Woodrow Benson, Thomas G. Gleason, Seema Mital, and Cecilia W. Lo
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bicuspid aortic valve ,coarctaction ,left ventricular outflow obstruction ,genetics ,protocadherin ,copy number variants ,Genetics ,QH426-470 - Abstract
Summary: Bicuspid aortic valve (BAV) with ∼1%–2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA). Mouse and human studies indicate LVOTO is genetically heterogeneous with a complex genetic etiology. Homozygous mutation in the Pcdha protocadherin gene cluster in mice can cause BAV, and also HLHS and other LVOTO phenotypes when accompanied by a second mutation. Here we show two common deletion copy number variants (delCNVs) within the PCDHA gene cluster are associated with LVOTO. Analysis of 1,218 white individuals with LVOTO versus 463 disease-free local control individuals yielded odds ratios (ORs) at 1.47 (95% confidence interval [CI], 1.13–1.92; p = 4.2 × 10−3) for LVOTO, 1.47 (95% CI, 1.10–1.97; p = 0.01) for BAV, 6.13 (95% CI, 2.75–13.7; p = 9.7 × 10−6) for CoA, and 1.49 (95% CI, 1.07–2.08; p = 0.019) for HLHS. Increased OR was observed for all LVOTO phenotypes in homozygous or compound heterozygous PCDHA delCNV genotype comparison versus wild type. Analysis of an independent white cohort (381 affected individuals, 1,352 control individuals) replicated the PCDHA delCNV association with LVOTO. Generalizability of these findings is suggested by similar observations in Black and Chinese individuals with LVOTO. Analysis of Pcdha mutant mice showed reduced PCDHA expression at regions of cell-cell contact in aortic smooth muscle and cushion mesenchyme, suggesting potential mechanisms for BAV pathogenesis and aortopathy. Together, these findings indicate common variants causing PCDHA deficiency play a significant role in the genetic etiology of common and rare LVOTO-CHD.
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- 2021
- Full Text
- View/download PDF
3. Prenatal Diagnosis of Aorto-Left Ventricular Tunnel With Dysplastic Bicuspid Aortic Valve: From Fetal Cardiac Failure to Favorable Outcome
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Ba Luu Truong, Anne Moreau De Bellaing, Emmanuelle Vialle, Ayman Haydar, Pascal Vouhe, Pierre Simon Jouk, and Gerard Blaysat
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prenatal diagnosis ,congenital heart defect ,aorto-left ventricular tunnel ,left ventricular function ,aortic regurgitation ,Pediatrics ,RJ1-570 - Abstract
Aorto-left ventricular tunnel (ALVT) is a rare congenital heart defect. Surgery has to be performed early to avoid life-threatening complications. Prenatal diagnosis of this defect is challenging. We report a case of ALVT diagnosed in a fetus showing premature severe cardiac failure at 24 GA. The new born was operated at day 3 of life with good results. Two years later, he is still doing well recovering a complete normal cardiac function. ALVT should be suggested in front of any fetal cardiac failure. Thanks to early diagnosis, prompt neonatal management can be organized and allows positive outcome.
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- 2020
- Full Text
- View/download PDF
4. Abnormal origin of the left pulmonary artery from the descending aorta and heterotaxy syndrome: an undescribed phenotypic association
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Anne Moreau de Bellaing, Damien Bonnet, and Lucile Houyel
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medicine.medical_specialty ,VACTERL Syndrome ,Aorta, Thoracic ,Heterotaxy Syndrome ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Anastomosis ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Abnormal Origin ,Internal medicine ,medicine.artery ,medicine ,Humans ,Lung ,Left aortic arch ,business.industry ,Infant, Newborn ,Infant ,Ductus Arteriosus ,General Medicine ,Left pulmonary artery ,Vascular surgery ,030228 respiratory system ,Descending aorta ,Pediatrics, Perinatology and Child Health ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Extensive screening in a newborn with prenatal suspicion of VACTERL syndrome identified an anomalous origin of the left pulmonary artery from the descending aorta with an arterial duct and left aortic arch, and normal intra-cardiac anatomy. Other anatomical anomalies suggested heterotaxy syndrome. At one-month-old, re-implantation of the 3.5 mm left pulmonary artery was performed by direct tension-low anastomosis. Post-operative course was complicated by severe left pulmonary atelectasis, and the patient died 20 days later.
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- 2021
5. Late Pediatric Mechanical Thrombectomy for Embolic Stroke as Bridge Reinforcement From LVAD to Heart Transplantation
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Charles-Joris Roux, Basile Kerleroux, Anne Moreau de Bellaing, Olivier Naggara, Jean-François Hak, Manoelle Kossorotoff, Lucile Houyel, Olivier Raisky, Gregoire Boulouis, and Damien Bonnet
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,heart ,030105 genetics & heredity ,03 medical and health sciences ,mechanical thrombectomy ,0302 clinical medicine ,Internal medicine ,medicine ,ischemic stroke ,left ventricular assist device ,Diseases of the circulatory (Cardiovascular) system ,cardiovascular diseases ,collateral circulation ,Heart transplantation ,business.industry ,Collateral circulation ,medicine.disease ,Embolic stroke ,CT, computed tomography ,Transplantation ,Mechanical thrombectomy ,Bridge (graph theory) ,pediatric ,Mini-Focus Issue: Vascular Medicine ,CICU, cardiac intensive care unit ,RC666-701 ,Ventricular assist device ,Heart failure ,MT, mechanical thrombectomy ,Cardiology ,LVAD, left ventricular assist device ,Case Report: Clinical Case ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,PedNISS, Pediatric National Institutes of Health Stroke Scale ,transplantation - Abstract
Although the left ventricular assist device is an important bridge to heart transplantation for patients with end-stage heart failure, it can also be a source of embolic stroke. We present a case of late intracranial mechanical thrombectomy performed for embolic stroke beyond the recommended 6 h, thus allowing for heart transplantation 4 days after intracranial mechanical thrombectomy. (Level of Difficulty: Advanced.), Central Illustration
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- 2021
6. Discovery of a genetic module essential for assigning left–right asymmetry in humans and ancestral vertebrates
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Emmanuelle Szenker-Ravi, Tim Ott, Muznah Khatoo, Anne Moreau de Bellaing, Wei Xuan Goh, Yan Ling Chong, Anja Beckers, Darshini Kannesan, Guillaume Louvel, Priyanka Anujan, Vydianathan Ravi, Carine Bonnard, Sébastien Moutton, Patric Schoen, Mélanie Fradin, Estelle Colin, André Megarbane, Linda Daou, Ghassan Chehab, Sylvie Di Filippo, Caroline Rooryck, Jean-François Deleuze, Anne Boland, Nicolas Arribard, Rukiye Eker, Sumanty Tohari, Alvin Yu-Jin Ng, Marlène Rio, Chun Teck Lim, Birgit Eisenhaber, Frank Eisenhaber, Byrappa Venkatesh, Jeanne Amiel, Hugues Roest Crollius, Christopher T. Gordon, Achim Gossler, Sudipto Roy, Tania Attie-Bitach, Martin Blum, Patrice Bouvagnet, Bruno Reversade, ACS - Heart failure & arrhythmias, ARD - Amsterdam Reproduction and Development, Genome Institute of Singapore (GIS), University of Hohenheim, Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Institute of Molecular and Cell Biology [Singapore, Singapore] (IMCB / A*STAR), National University Hospital [Singapore] (NUH), Centre Hospitalier Universitaire de Liège (CHU-Liège), Hannover Medical School [Hannover] (MHH), REBIRTH Cluster of Excellence [Hannover], Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hammersmith Hospital NHS Imperial College Healthcare, Skin Research Institute of Singapore [Singapore, Singapore] (SRIS / A*STAR), Maison de Santé Protestante de Bordeaux-Bagatelle (MSPB), Praxis Dr Patric SCHÖN [Oberschleissheim, Germany] (2PS), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Gilbert and Rose-Marie Chagoury School of Medicine [Lebanese American University], Lebanese American University (LAU), Institut Jérôme Lejeune, Université Saint-Joseph de Beyrouth (USJ), Lebanese University [Beirut] (LU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Istanbul University, Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Singapore Institute of Food and Biotechnology Innovation [Singapore, Singapore] (SIFBI / A*STAR ), Bioinformatics Institute [Singapore, Singapore] (BII / A*STAR), Nanyang Technological University [Singapour], National University of Singapore (NUS), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Maison de la Femme de la Mère et de l'Enfant [CHU de la Martinique] (MFME [Fort de France]), CHU de la Martinique [Fort de France], Koc University School of Medicine [Istanbul, Turkey] (KUSOM), and CarMeN, laboratoire
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[SDV] Life Sciences [q-bio] ,Loss of Function Mutation ,[SDV]Life Sciences [q-bio] ,Vertebrates ,Metalloproteases ,Genetics ,Animals ,Humans ,Proteins ,Gene Regulatory Networks ,Cilia ,Biological Evolution ,Body Patterning - Abstract
Erratum in Publisher Correction: Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates. Szenker-Ravi E, Ott T, Khatoo M, Moreau de Bellaing A, Goh WX, Chong YL, Beckers A, Kannesan D, Louvel G, Anujan P, Ravi V, Bonnard C, Moutton S, Schoen P, Fradin M, Colin E, Megarbane A, Daou L, Chehab G, Di Filippo S, Rooryck C, Deleuze JF, Boland A, Arribard N, Eker R, Tohari S, Ng AY, Rio M, Lim CT, Eisenhaber B, Eisenhaber F, Venkatesh B, Amiel J, Crollius HR, Gordon CT, Gossler A, Roy S, Attie-Bitach T, Blum M, Bouvagnet P, Reversade B.Nat Genet. 2022 Jun;54(6):906. doi: 10.1038/s41588-022-01053-8.PMID: 35304595 No abstract available.; International audience; The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.
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- 2022
7. Common deletion variants causing protocadherin-α deficiency contribute to the complex genetics of BAV and left-sided congenital heart disease
- Author
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William T. Mahle, D. Woodrow Benson, Paul M. Kirshbom, Dennis M. McNamara, Nathan Salamacha, William A. Devine, Anne Moreau de Bellaing, Julie A. Phillippi, Thomas G. Gleason, Michael X. Wang, George C. Gabriel, Vidu Garg, Carrie Lee, Anastasia Miron, Wenjuan Zhu, Yijen L. Wu, Lazaros Kochilas, Cullen B. Young, Tuantuan Tan, Yihua He, Abha S. Bais, Jianhua Xing, Jonathan Klonowski, Hung Sing Li, Jianbin Wang, Peter White, Marie Billaud, Polakit Teekakirikul, Jingyu Zhang, Kylia Williams, Jiuann-huey Lin, Seema Mital, Leonid Emerel, Samuel K. Wyman, Tara D. Richards, Ankur Saini, Cecilia W. Lo, Erik Fung, Kim L. McBride, Jennifer C. Hill, and Lisa J. Martin
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medicine.medical_specialty ,bicuspid aortic valve ,Heart disease ,Genetic heterogeneity ,business.industry ,Coarctation of the aorta ,QH426-470 ,medicine.disease ,Compound heterozygosity ,Article ,Hypoplastic left heart syndrome ,Pathogenesis ,Bicuspid aortic valve ,Internal medicine ,Genetics ,medicine ,Cardiology ,left ventricular outflow obstruction ,Molecular Medicine ,Ventricular outflow tract ,protocadherin ,business ,Genetics (clinical) ,coarctaction ,copy number variants - Abstract
Summary Bicuspid aortic valve (BAV) with ∼1%–2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA). Mouse and human studies indicate LVOTO is genetically heterogeneous with a complex genetic etiology. Homozygous mutation in the Pcdha protocadherin gene cluster in mice can cause BAV, and also HLHS and other LVOTO phenotypes when accompanied by a second mutation. Here we show two common deletion copy number variants (delCNVs) within the PCDHA gene cluster are associated with LVOTO. Analysis of 1,218 white individuals with LVOTO versus 463 disease-free local control individuals yielded odds ratios (ORs) at 1.47 (95% confidence interval [CI], 1.13–1.92; p = 4.2 × 10−3) for LVOTO, 1.47 (95% CI, 1.10–1.97; p = 0.01) for BAV, 6.13 (95% CI, 2.75–13.7; p = 9.7 × 10−6) for CoA, and 1.49 (95% CI, 1.07–2.08; p = 0.019) for HLHS. Increased OR was observed for all LVOTO phenotypes in homozygous or compound heterozygous PCDHA delCNV genotype comparison versus wild type. Analysis of an independent white cohort (381 affected individuals, 1,352 control individuals) replicated the PCDHA delCNV association with LVOTO. Generalizability of these findings is suggested by similar observations in Black and Chinese individuals with LVOTO. Analysis of Pcdha mutant mice showed reduced PCDHA expression at regions of cell-cell contact in aortic smooth muscle and cushion mesenchyme, suggesting potential mechanisms for BAV pathogenesis and aortopathy. Together, these findings indicate common variants causing PCDHA deficiency play a significant role in the genetic etiology of common and rare LVOTO-CHD.
- Published
- 2021
8. PPA2-associated sudden cardiac death
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Charlotte V. Y. Knowles, Anil Kanthi, Carolyn Tysoe, Georgia Spentzou, Claire L. S. Turner, Jan A Till, Liza K. Phillips, Anne Moreau de Bellaing, Diptendu Chatterjee, Alexandre Janin, Paul French, Tamara T. Koopmann, Anju Shukla, Melanie T. Achleitner, Loïc de Pontual, Matthew S. Edwards, Deborah J. Morris-Rosendahl, Noha Elserafy, Kirti Mittal, Jessie Cameron, Wendy K. Chung, Saskia B. Wortmann, Sajel L Kana, Kit Doudney, Robert G. Weintraub, Peter M George, Priyanka Ahimaz, Kyla Dunn, Ona Faye-Petersen, Katta M. Girisha, Hannah L. Kennedy, Kate S Lichkus, Alexa Kidd, Sumith Parikh, Jason D. Merker, Megan E. Grove, Ruth McGowan, Laura Brett, Anna C.E. Hurst, Jeanne Amiel, Bindu Parayil Sankaran, Dianna G. Fisk, Clémantine Dimartino, Charlotte L. Alston, Michelle L. Thompson, Johannes A. Mayr, Tessa Homfray, Alan Ma, Robert McFarland, Muhammad A Rafiq, Anne Guimier, Robert M Hamilton, Christian Turner, Karen McLeod, Christopher T. Gordon, Robert W. Taylor, David R. Thorburn, Florence van den Broek, Carolyn Ellaway, and Fanny Bajolle
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Neurological signs ,medicine.medical_specialty ,Adolescent ,Cardiomyopathy ,Disease ,Article ,Sudden cardiac death ,Mitochondrial Proteins ,Internal medicine ,Humans ,Medicine ,Allele ,Alleles ,Genetics (clinical) ,Genetics & Heredity ,0604 Genetics ,Science & Technology ,business.industry ,Sudden cardiac arrest ,1103 Clinical Sciences ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,medicine.disease ,DEFICIENCY ,Inorganic Pyrophosphatase ,Death, Sudden, Cardiac ,Child, Preschool ,Heart failure ,Mutation ,Alcohol intake ,medicine.symptom ,Cardiomyopathies ,business ,Life Sciences & Biomedicine - Abstract
Purpose Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants. Methods Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. Results Among the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity. Conclusion We expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.
- Published
- 2021
9. Genetic resiliency associated with dominant lethal
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Polakit, Teekakirikul, Wenjuan, Zhu, Xinxiu, Xu, Cullen B, Young, Tuantuan, Tan, Amanda M, Smith, Chengdong, Wang, Kevin A, Peterson, George C, Gabriel, Sebastian, Ho, Yi, Sheng, Anne, Moreau de Bellaing, Daniel A, Sonnenberg, Jiuann-Huey, Lin, Elisavet, Fotiou, Gennadiy, Tenin, Michael X, Wang, Yijen L, Wu, Timothy, Feinstein, William, Devine, Honglan, Gou, Abha S, Bais, Benjamin J, Glennon, Maliha, Zahid, Timothy C, Wong, Ferhaan, Ahmad, Michael J, Rynkiewicz, William J, Lehman, Bernard, Keavney, Tero-Pekka, Alastalo, Mary-Louise, Freckmann, Kyle, Orwig, Steve, Murray, Stephanie M, Ware, Hui, Zhao, Brian, Feingold, and Cecilia W, Lo
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Talin ,Mice ,Myofibrils ,Microfilament Proteins ,Mutation ,Animals ,Humans ,Tropomyosin ,Heart Septal Defects, Atrial ,Pedigree - Abstract
Analysis of large-scale human genomic data has yielded unexplained mutations known to cause severe disease in healthy individuals. Here, we report the unexpected recovery of a rare dominant lethal mutation in
- Published
- 2021
10. Genetic Resiliency Associated With Dominant Lethal TPM1 Mutation Causing Atrial Septal Defect With High Heritability
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Gennadiy Tenin, Sebastian Ho, Amanda M. Smith, Abha S. Bais, Xinxiu Xu, Yi Sheng, Tuantuan Tan, William Lehman, Brian Feingold, Kevin A. Peterson, Stephanie M. Ware, Mary-Louise Freckmann, Steve Murray, Anne Moreau de Bellaing, George C. Gabriel, Kyle E. Orwig, Hui Zhao, Ferhaan Ahmad, Cecilia W. Lo, Tero-Pekka Alastalo, Michael J. Rynkiewicz, Elisavet Fotiou, Wenjuan Zhu, Cullen B. Young, Chengdong Wang, Maliha Zahid, Daniel Sonnenberg, Timothy N. Feinstein, Polakit Teekakirikul, Jiuanne-huey Lin, Yijen L. Wu, Timothy C. Wong, Honglan Gou, William A. Devine, Bernard Keavney, and Michael X. Wang
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Pathogenesis ,Genetics ,Fetus ,Myofibril assembly ,Myofilament ,Mutation ,medicine ,TPM1 ,Biology ,Induced pluripotent stem cell ,medicine.disease_cause ,Embryonic stem cell - Abstract
Analysis of large scale human genomic data has yielded unexplained mutations known to cause severe disease in healthy individuals. Here we report the unexpected recovery of a rare dominant lethal mutation in TPM1, a sarcomeric actin-binding protein, in 8 individuals with large atrial septal defect (ASD) in a 5-generation pedigree. Mice with TPM1 mutation exhibited early embryonic lethality with disrupted myofibril assembly and no heartbeat. However, patient induced pluripotent stem cell derived cardiomyocytes showed normal beating with mild myofilament defect, indicating disease suppression. A variant in TLN2, another myofilament actin-binding protein, was identified as a candidate suppressor. Mouse CRISRP knockin of both the TLN2/TPM1 variants rescued heart beating, with near term fetuses exhibiting large ASD. Thus, the role of TPM1 in ASD pathogenesis unfolded with the suppression of its embryonic lethality by a TLN2 protective variant. These findings provide evidence that genetic resiliency can arise with genetic suppression of a deleterious mutation.
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- 2021
11. Publisher Correction: Discovery of a genetic module essential for assigning left–right asymmetry in humans and ancestral vertebrates
- Author
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Emmanuelle Szenker-Ravi, Tim Ott, Muznah Khatoo, Anne Moreau de Bellaing, Wei Xuan Goh, Yan Ling Chong, Anja Beckers, Darshini Kannesan, Guillaume Louvel, Priyanka Anujan, Vydianathan Ravi, Carine Bonnard, Sébastien Moutton, Patric Schoen, Mélanie Fradin, Estelle Colin, André Megarbane, Linda Daou, Ghassan Chehab, Sylvie Di Filippo, Caroline Rooryck, Jean-François Deleuze, Anne Boland, Nicolas Arribard, Rukiye Eker, Sumanty Tohari, Alvin Yu-Jin Ng, Marlène Rio, Chun Teck Lim, Birgit Eisenhaber, Frank Eisenhaber, Byrappa Venkatesh, Jeanne Amiel, Hugues Roest Crollius, Christopher T. Gordon, Achim Gossler, Sudipto Roy, Tania Attie-Bitach, Martin Blum, Patrice Bouvagnet, and Bruno Reversade
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Genetics - Published
- 2022
12. Genetic resiliency associated with dominant lethal TPM1 mutation causing atrial septal defect with high heritability
- Author
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Polakit Teekakirikul, Wenjuan Zhu, Xinxiu Xu, Cullen B. Young, Tuantuan Tan, Amanda M. Smith, Chengdong Wang, Kevin A. Peterson, George C. Gabriel, Sebastian Ho, Yi Sheng, Anne Moreau de Bellaing, Daniel A. Sonnenberg, Jiuann-huey Lin, Elisavet Fotiou, Gennadiy Tenin, Michael X. Wang, Yijen L. Wu, Timothy Feinstein, William Devine, Honglan Gou, Abha S. Bais, Benjamin J. Glennon, Maliha Zahid, Timothy C. Wong, Ferhaan Ahmad, Michael J. Rynkiewicz, William J. Lehman, Bernard Keavney, Tero-Pekka Alastalo, Mary-Louise Freckmann, Kyle Orwig, Steve Murray, Stephanie M. Ware, Hui Zhao, Brian Feingold, and Cecilia W. Lo
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General Biochemistry, Genetics and Molecular Biology - Published
- 2022
13. Heterotaxy: fluctuat nec mergitur
- Author
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Damien Bonnet, Anne Moreau de Bellaing, and Lucile Houyel
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0301 basic medicine ,Atrial Appendage ,Dextrocardia ,Heterotaxy Syndrome ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,In patient ,Child ,business.industry ,General Medicine ,Anatomy ,Situs Inversus ,medicine.disease ,Situs inversus ,030104 developmental biology ,Visceral Heterotaxy ,Pediatrics, Perinatology and Child Health ,Cardiology and Cardiovascular Medicine ,business ,Heterotaxy - Abstract
The International Pediatric and Congenital Cardiac Code (IPCCC) states thatvisceral heterotaxyis defined as “a congenital malformation in which the internal thoraco-abdominal organs demonstrate abnormal arrangement across the left-right axis of the body. By convention, in congenital cardiology, heterotaxy syndrome does not include patients with complete mirror-imaged arrangement of the internal organs along the left-right axis also known as “total mirror imagery” or “situs inversus totalis”.” [www.ipccc.net]In patients with heterotaxy, it is important to describe both the cardiac relations and the junctional connections of the cardiac segments, with documentation of the arrangement of the atrial appendages, the ventricular topology, the nature of the unions of the segments across the atrioventricular and the ventriculoarterial junctions, the infundibular morphologies, and the relationships of the arterial trunks in space. Particular attention is required for the venoatrial connections, since these are so often abnormal. The relationship and arrangement of the remaining thoraco-abdominal organs, including the lungs, the spleen, the liver, and the intestines, also must be described separately, because, although common patterns of association have been identified, there are frequent exceptions to these common patterns. Therefore, in patients with heterotaxy, it is important to describe each thoracic and abdominal organ independently.
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- 2021
14. A Membrane-Tethered Ubiquitination Pathway Regulates Hedgehog Signaling and Heart Development
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Teresa M. Gunn, L. Aravind, Tejas S. Athni, Arunkumar Krishnan, Anne Moreau de Bellaing, William A. Devine, Jennifer H. Kong, Rajat Rohatgi, Sebastian Ho, Jiuann-Huey Ivy Lin, Chandni B. Patel, Cecilia W. Lo, Cullen B. Young, and Ganesh V. Pusapati
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Ubiquitin-Protein Ligases ,Gene Dosage ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Ubiquitin ,Animals ,Hedgehog Proteins ,Molecular Biology ,Hedgehog ,Alleles ,030304 developmental biology ,0303 health sciences ,biology ,Ubiquitination ,Membrane Proteins ,Epistasis, Genetic ,Heart ,Cell Biology ,Embryo, Mammalian ,Smoothened Receptor ,Transmembrane protein ,Hedgehog signaling pathway ,Ubiquitin ligase ,Cell biology ,Phenotype ,Ubiquitin ligase complex ,Mutation ,biology.protein ,NIH 3T3 Cells ,Smoothened ,030217 neurology & neurosurgery ,Developmental Biology ,Morphogen ,Protein Binding ,Signal Transduction - Abstract
The etiology of congenital heart defects (CHDs), which are among the most common human birth defects, is poorly understood because of its complex genetic architecture. Here, we show that two genes implicated in CHDs, Megf8 and Mgrn1, interact genetically and biochemically to regulate the strength of Hedgehog signaling in target cells. MEGF8, a transmembrane protein, and MGRN1, a RING superfamily E3 ligase, assemble to form a receptor-like ubiquitin ligase complex that catalyzes the ubiquitination and degradation of the Hedgehog pathway transducer Smoothened. Homozygous Megf8 and Mgrn1 mutations increased Smoothened abundance and elevated sensitivity to Hedgehog ligands. While mice heterozygous for loss-of-function Megf8 or Mgrn1 mutations were normal, double heterozygous embryos exhibited an incompletely penetrant syndrome of CHDs with heterotaxy. Thus, genetic interactions can arise from biochemical mechanisms that calibrate morphogen signaling strength, a conclusion broadly relevant for the many human diseases in which oligogenic inheritance is emerging as a mechanism for heritability.
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- 2020
15. A ubiquitin-based mechanism for the oligogenic inheritance of heterotaxy and heart defects
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William A. Devine, Cecilia W. Lo, Anne Moreau de Bellaing, L. Aravind, Rajat Rohatgi, Sebastian Ho, Ganesh V. Pusapati, Chandni B. Patel, Jiuann-Huey Ivy Lin, Arunkumar Krishnan, Teresa M. Gunn, Tejas S. Athni, Cullen B. Young, and Jennifer H. Kong
- Subjects
Ubiquitin ,biology ,Ubiquitin ligase complex ,biology.protein ,Oligogenic Inheritance ,Smoothened ,Hedgehog ,Hedgehog signaling pathway ,Cell biology ,Ubiquitin ligase ,Morphogen - Abstract
The etiology of congenital heart defects (CHDs), amongst the most common human birth defects, is poorly understood partly because of its complex genetic architecture. Here we show that two genes previously implicated in CHDs, Megf8 and Mgrn1, interact genetically and biochemically to regulate the strength of Hedgehog signaling in target cells. MEGF8, a single-pass transmembrane protein, and MGRN1, a RING superfamily E3 ligase, assemble to form a transmembrane ubiquitin ligase complex that catalyzes the ubiquitination and degradation of the Hedgehog pathway transducer Smoothened. Homozygous Megf8 and Mgrn1 mutations increased Smoothened abundance and elevated sensitivity to Hedgehog ligands. While mice heterozygous for loss-of-function Megf8 or Mgrn1 mutations were normal, double heterozygous embryos exhibited an incompletely penetrant syndrome of CHDs with heterotaxy. Thus, genetic interactions between components of a receptor-like ubiquitin ligase complex that tunes morphogen signaling strength can cause a birth defect syndrome inherited in an oligogenic pattern.
- Published
- 2020
16. Perinatal intracardiac teratoma: unusual presentation and review of the literature
- Author
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Damien Bonnet, Lucile Houyel, and Anne Moreau de Bellaing
- Subjects
Male ,Surgical resection ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Heart Ventricles ,Ultrasonography, Prenatal ,Intracardiac injection ,Extracorporeal ,Diagnosis, Differential ,Heart Neoplasms ,Fatal Outcome ,Pregnancy ,medicine ,Humans ,cardiovascular diseases ,Fetus ,business.industry ,Infant, Newborn ,Teratoma ,General Medicine ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Echocardiography ,Ventricle ,Pediatrics, Perinatology and Child Health ,cardiovascular system ,Female ,Presentation (obstetrics) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Intracardiac teratomas are rare primary tumours. We report the case of an infant prenatally diagnosed with an isolated multi-cystic mass developed in the right ventricle causing neonatal refractory ventricular arrhythmia. Despite rescue extracorporeal support and partial surgical resection, he died as almost all the previous reported perinatal intracardiac teratomas whatever the prenatal tolerance and the size of the tumour. The common poor outcome of fetal intracardiac teratomas should be known when counselling parents during pregnancy.
- Published
- 2019
17. ECMO in newborns after congenital heart surgery: Short- and mid-term outcome
- Author
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Olivier Raisky, India Pottier, and Anne Moreau de Bellaing
- Subjects
medicine.medical_specialty ,business.industry ,medicine ,Cardiology and Cardiovascular Medicine ,business ,Outcome (game theory) ,Term (time) ,Surgery - Published
- 2021
18. Palliative arterial switch and pulmonary banding for complex intra cardiac repair in transposition of the great arteries
- Author
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Margaux Pontaillier, Vanessa Lopez, Anne Moreau de Bellaing, Régis Gaudin, Ayman Haydar, Pascal Vouhé, Olivier Raisky, and Célia Gran
- Subjects
Aortic valve ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,business.industry ,Retrospective cohort study ,medicine.disease ,Intensive care unit ,Intracardiac injection ,Hypoplasia ,Pulmonary artery banding ,law.invention ,medicine.anatomical_structure ,Great arteries ,law ,Internal medicine ,Cardiology ,medicine ,Cardiac skeleton ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aim Transposition of the great arteries (TGA) associated with ventricular septal defect (VSD) could present an intracardiac anatomy making the neonatal repair very challenging: multiple/apical VSD, straddling, tortuous intraventricular tunnel repair. To delay the repair, the isolated pulmonary artery banding (PAB) has the disadvantage to endanger the future aortic valve and to create a double obstacle in the frequent association with aortic annulus and arch hypoplasia. We propose a 2-step strategy with an initial palliative arterial switch operation (ASO) associated with PAB (± aortic arch repair) and, later, an intracardiac repair with debanding. The Aim of this retrospective study is to compare this strategy to a classic isolated PAB. Methods Among the 715 neonatal TGA admitted in our institution between 2007 and 2018, 10 complex TGA benefited either from a palliative ASO with PAB (group A, n = 5) or a PAB (group B, n = 5). Results At palliation, the duration of inotropic support and the length of stay in intensive care unit were significantly shorter in group A (respectively 4.75 ± 1.7 and 5.5 [4.25–6.75] days versus 13 ± 6.9 and 16 [10.5–30] days in group B; P = 0,029 and P = 0,008). At complete repair, age and weight were significantly higher in group A (P = 0,018) and the aortic cross-clamping and bypass times were shorter (P = 0,018). No patient required a delayed sternal closure in group A. Mean length of stay in intensive care unit and hospital duration were respectively of 2 ± 1 days and 5.6 ± 1.53 days in group A versus 21.4 ± 16.9 days and 24.5 ± 19.9 days in the group B (P = 0.018 and P = 0.029), showing reduced morbidity. Conclusion Differing the neonatal repair for TGA is exceptional. When we should consider it due to particular intracardiac anatomy, it seems legitimate to practice a palliative ASO rather than the classic isolated PAB.
- Published
- 2021
19. Anomalous aortic origin of coronary arteries: an alternative to the unroofing strategy
- Author
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Pascal Vouhé, Damien Bonnet, Régis Gaudin, Ayman Haydar, Pichoy Danial, Olivier Raisky, Margaux Pontailler, Sophie Malekzadeh-Milani, Anne Moreau de Bellaing, Maïra Gaillard, Leonora du Puy-Montbrun, and Bari Murtuza
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Chest Pain ,Adolescent ,medicine.medical_treatment ,Coronary Vessel Anomalies ,Chest pain ,Sudden death ,Sudden cardiac death ,Coronary artery bypass surgery ,Young Adult ,Angioplasty ,medicine ,Humans ,Child ,Aorta ,business.industry ,General Medicine ,medicine.disease ,Surgery ,Coronary arteries ,Ostium ,medicine.anatomical_structure ,Anomalous aortic origin of a coronary artery ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVES Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden death in children and young adults. The most threatening anatomy is an interarterial and an intramural course, both probably involved in ischaemic phenomena and sudden death. The treatment of interarterial AAOCA remains controversial. Most of the published studies describe the results of the unroofing technique. Our study aims to evaluate the results of a different surgical approach. METHODS From 2005 to 2019, 61 patients were operated on for an interarterial AAOCA (median age 14.7 years). Forty patients had a right AAOCA, and 21 patients had a left AAOCA including 5 patients with intraseptal course. Seventy percent of patients were symptomatic. Five patients had an aborted sudden cardiac death. Two surgical techniques were used: an ‘anatomical’ repair for 35 patients (15 left and 22 right AAOCA) or a coronary translocation with creation of a neo-ostia in 19 patients (1 left and 18 right AAOCA). The 5 left AAOCA patients with an intra-septal course required a complete release of the coronary artery from the septum. RESULTS There was no early or late postoperative death. Three patients had an acute postoperative ischaemic event. Two patients required immediate angioplasty and stenting: 1 patient (7 years) with a hypoplastic right AAOCA and 1 patient (66 years) for inadequate tailoring after septal release. The third patient required an immediate surgical revision (H-2) for left AAOCA thrombosis at the level of the pericardial patch with full myocardial recovery at discharge. During follow-up, 1 patient with right AAOCA translocation and chronic chest pain required subsequent stenting and finally a coronary artery bypass grafting 2 years after initial surgery. One patient who had an asymptomatic mild right coronary stenosis 1 year after anatomical repair was successfully treated by angioplasty alone. All patients but 1 who underwent coronary translocation are totally asymptomatic. All patients with anatomical repair or septal release are free from ischaemic symptoms. CONCLUSIONS Anatomical repair might provide a better protective option for these patients. Unlike unroofing, it treats the entire intramural segment, relocates the ostium at the appropriate sinus level and corrects any acute take-off angle.
- Published
- 2019
20. Ascending aorta and aortic root replacement (with or without valve sparing) in early childhood: surgical strategies and long-term outcomes
- Author
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Pascal Vouhé, Anne Moreau de Bellaing, Margaux Pontailler, Olivier Raisky, Ayman Haydar, Régis Gaudin, Fanny Bajolle, Damien Bonnet, and Bari Murtuza
- Subjects
Pulmonary and Respiratory Medicine ,Marfan syndrome ,medicine.medical_specialty ,Aortic Valve Insufficiency ,030204 cardiovascular system & hematology ,Marfan Syndrome ,Blood Vessel Prosthesis Implantation ,03 medical and health sciences ,0302 clinical medicine ,Aortic valve replacement ,Interquartile range ,medicine.artery ,Ascending aorta ,Humans ,Medicine ,Cardiac skeleton ,Child ,Aorta ,Aortic valve regurgitation ,Retrospective Studies ,business.industry ,Mortality rate ,General Medicine ,medicine.disease ,Surgery ,Treatment Outcome ,030228 respiratory system ,Aortic Valve ,Child, Preschool ,Replantation ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVESAortic root and ascending aorta replacements (AARs) are rarely required in the paediatric population. We report here a series of AAR performed in young children using different surgical techniques.METHODSBetween 1995 and 2017, 32 children under the age of 10 years (median age 5.4 years) underwent AAR procedures at our institution. Twenty-two (69%) had a connective tissue disease (infantile Marfan syndrome or Loeys–Dietz syndrome). We performed 11 AAR using a composite graft with a mechanical prosthesis and 21 valve-sparing procedures (10 Yacoub operations and 11 David operations). Median follow-up for operative survivors was 7.7 years (interquartile range 4.2–12.8 years).RESULTSThe cardiac-related early mortality rate was 6%. Patient survival was 91% at both 1 and 10 years. Eleven survivors (38%), all with a status of post-valve-sparing procedure, required an aortic root reintervention with an aortic valve replacement after a median interval of 4.2 years. Interestingly, only patients with infantile Marfan syndrome tended to be associated with risk of reoperation.CONCLUSIONSAortic root and AARs are safe in young children whatever the surgical procedure. Aortic valve-sparing procedures show good long-term results except in children with infantile Marfan syndrome whose ineluctable aortic annulus dilatation or aortic valve regurgitation requires reintervention after a short period.
- Published
- 2019
21. Surgical repair of concomitant ventricular septal defect and aortic cusp prolapse or aortic regurgitation, also known as the Laubry-Pezzi syndrome
- Author
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Régis Gaudin, Margaux Pontailler, Olivier Raisky, and Anne Moreau de Bellaing
- Subjects
Aortic valve ,Surgical repair ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,business.industry ,Masters of Cardiothoracic Surgery ,Regurgitation (circulation) ,030204 cardiovascular system & hematology ,Aortic Valve Prolapse ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030228 respiratory system ,Concomitant ,Internal medicine ,Materials Chemistry ,cardiovascular system ,medicine ,Cardiology ,Cusp (anatomy) ,Surgery ,In patient ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business - Abstract
It has been almost a century since Charles Laubry and Cesare Pezzi first described the clinical features of aortic regurgitation (AR) due to aortic valve prolapse in patients with ventricular septal defects (VSDs) (1). The Venturi effect is the explanation to Laubry-Pezzi syndrome: a significant fall in pressure when blood flows through the VSD under the aortic valve, sucking either the right or the non-coronary leaflet in the VSD, resulting in AR. It is most commonly found in infundibular VSDs but can also be encountered with perimembranous VSDs.
- Published
- 2019
22. Tetralogy of Fallot and abnormal coronary artery: use of a prosthetic conduit is outdated
- Author
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Chloé Bernard, Damien Bonnet, Margaux Pontailler, Olivier Raisky, Mansour Mostefa Kara, Claudio Barbanti, Pascal Vouhé, Régis Gaudin, Anne Moreau de Bellaing, and Ayman Haydar
- Subjects
Pulmonary and Respiratory Medicine ,Male ,Reoperation ,medicine.medical_specialty ,Adolescent ,Coronary Vessel Anomalies ,Heart Ventricles ,Pulmonary Artery ,Risk Factors ,Internal medicine ,Pulmonary Valve Replacement ,medicine ,Ventricular outflow tract ,Humans ,Cardiac Surgical Procedures ,Child ,Tetralogy of Fallot ,Retrospective Studies ,Pulmonary Valve ,business.industry ,Infant ,General Medicine ,medicine.disease ,Blood Vessel Prosthesis ,Stenosis ,medicine.anatomical_structure ,Treatment Outcome ,Ventricle ,Pulmonary valve ,Child, Preschool ,Cardiology ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,Commissurotomy ,business ,Artery - Abstract
OBJECTIVESRepair of tetralogy of Fallot (ToF) can be challenging in the presence of an abnormal coronary artery (CA) in 5–12% of cases. The aim of this study was to report our experience with ToF repair without the systematic use of a right ventricle-to-pulmonary artery (RV-PA) conduit.METHODSWe conducted a monocentric retrospective study from 2000 to 2016, including 943 patients with ToF who underwent biventricular repair, of whom 8% (n = 76) presented with an abnormal CA. Mean follow-up time was 50 months (1 month–18 years).RESULTSThe most frequent CA anomaly was the left descending artery arising from the right CA (n = 47, 61.8%). The median age at repair was 7.7 months (1.8 months–16 years). Thirteen patients (17%) required prior palliation, mostly systemic pulmonary shunts for anoxic spells in the neonatal period. Surgical repair allowed us to preserve the annulus in 40 patients (53%) by combining PA trunk plasty, commissurotomy and infundibulotomy under the abnormal CA. If the annulus had to be opened (n = 35, 46%), a transannular patch was inserted after a vertical incision of the PA trunk and extended obliquely on the RV over the anomalous crossing CA (with an infundibulotomy under the abnormal CA). Three patients (4%) required the insertion of an RV-PA conduit (1 valved tube and 2 RV-PA GORE-TEX tubes with annulus conservation). The early mortality rate was 4% (n = 3); none of the deaths was coronary related. Four patients (5%) required reoperation (2 early and 2 late reoperations) for residual pulmonary stenosis, 3 of whom had annulus preservation during the initial repair. The mean RV/left ventricle (LV) pressure ratio and an RV/LV pressure ratio >2/3 were identified as risk factors for right ventricular outflow tract (RVOT) reinterventions (P = 0.0026, P = 0.0085, respectively), RVOT reoperations (P = 0.0002 for both) and reoperation for RVOT residual stenosis (P = 0.0002, P = 0.0014, respectively). Two patients underwent pulmonary valve replacement. Freedom from late reoperation was 100% at 1 year, 97% at 5 years and 84% at 10 and 15 years.CONCLUSIONSRepair of ToF and abnormal CA can be performed without an RV-PA conduit, with an acceptable low reintervention rate. The high early mortality rate in this series remains a concern. If any doubt remains about the surgical relief of the RVOT obstruction, the RV/LV pressure ratio should always be measured in the operating room.
- Published
- 2018
23. Double orifice and atrioventricular septal defect: dealing with the zone of apposition†
- Author
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Moussa Haidar, Margaux Pontailler, Régis Gaudin, Pamela Moceri, Pascal Vouhé, Olivier Metton, Damien Bonnet, Lucile Houyel, Anne Moreau de Bellaing, Mathilde Méot, and Olivier Raisky
- Subjects
Pulmonary and Respiratory Medicine ,Male ,Reoperation ,medicine.medical_specialty ,medicine.medical_treatment ,Regurgitation (circulation) ,Preoperative care ,Mitral valve ,medicine ,Humans ,Cardiac Surgical Procedures ,Papillary muscle ,Retrospective Studies ,Surgical repair ,Atrioventricular valve ,Mitral valve repair ,business.industry ,Heart Septal Defects ,Mitral valve replacement ,Infant ,General Medicine ,Surgery ,medicine.anatomical_structure ,Female ,Tricuspid Valve ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVESA double orifice of the left atrioventricular valve (LAVV) associated with atrioventricular septal defects (AVSD) can significantly complicate surgical repair. This study reports our experience of AVSD repair over 3 decades, with special attention to the zone of apposition (ZoA) of the main orifice, and presents a technique of hemivalve pericardial extension in specific situations.METHODSWe performed a retrospective study from 1987 to 2016 on 1067 patients with AVSD of whom 43 (4%) had a double orifice, plus 2 additional patients who required LAVV pericardial enlargement. Median age at repair was 1.3 years. Mean follow-up was 8.2 years (1 month–32 years).RESULTSAssociated abnormalities of the LAVV subvalvular apparatus were found in 7 patients (5 parachute LAVV and 2 absence of LAVV subvalvular apparatus). ZoA was noted in 4 patients (9%): partially closed in 15 (35%) and completely closed in 24 (56%). Four patients required, either at first repair or secondarily, a hemivalve enlargement using a pericardial patch without closure of the ZoA. The early mortality rate was 7% (n = 3), all before 2000. Two patients had unbalanced ventricles and the third had a single papillary muscle. There were no late deaths. Six patients (14%) required 7 reoperations (3 early and 4 late reoperations) for LAVV regurgitation and/or dysfunction, of whom 4 (9%) required mechanical LAVV replacement (all before 2000). Freedom from late LAVV reoperation was 97% at 1 year, 94% at 5 years and 87% at 10, 20 and 30 years. Unbalanced ventricles (P = 0.045), subvalvular abnormalities (P = 0.0037) and grade >2 LAVV postoperative regurgitation (P = 0.017) were identified as risk factors for LAVV reoperations. Freedom from LAVV mechanical valve replacement was 95% at 1 year, 90% at 5 years and 85% at 10, 20 and 30 years. An anomalous LAVV subvalvular apparatus was identified as a risk factor for mechanical valve replacement (P = 0.010). None of the patients who underwent LAVV pericardial extension had significant LAVV regurgitation at the last follow-up examination.CONCLUSIONSRepair of AVSD and double orifice can be tricky. Preoperative LAVV regurgitation was not identified as an independent predictor of surgical outcome. LAVV hemivalve extension appears to be a useful and effective alternate surgical strategy when the ZoA cannot be closed.
- Published
- 2018
24. Mitral valve replacement with a pulmonary autograft: long-term follow-up in an infant
- Author
-
Amel Mathiron, Yves Lecompte, Anne Moreau de Bellaing, and Pascal Vouhé
- Subjects
Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Complete atrioventricular septal defect ,Time Factors ,Long term follow up ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Prosthesis Design ,Prosthesis ,03 medical and health sciences ,0302 clinical medicine ,Mitral valve ,medicine ,Humans ,cardiovascular diseases ,Autografts ,Heart Valve Prosthesis Implantation ,Pulmonary Valve ,business.industry ,Ross procedure ,Modified technique ,Mitral valve replacement ,Infant ,Mitral Valve Insufficiency ,Surgery ,medicine.anatomical_structure ,030228 respiratory system ,Echocardiography ,cardiovascular system ,Mitral Valve ,Cardiology and Cardiovascular Medicine ,Left atrioventricular valve regurgitation ,business ,Follow-Up Studies - Abstract
A 7-month-old boy with a complete atrioventricular septal defect presented with severe left atrioventricular valve regurgitation 4 months after complete repair. As the valve was unsuitable for the repair and the annulus was too small to accommodate a mechanical prosthesis, the modified mitral Ross operation was performed. The long-term outcome was uneventful for 12 years. The mitral Ross procedure is an old-described technique in which classically the pulmonary autograft is encased in a prosthetic conduit preventing any growth potential. On the contrary, the modified technique used in this case shows that the long-term function can be obtained. This procedure may be a valuable option when mitral valve replacement is necessary in infants.
- Published
- 2018
25. MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates
- Author
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Cecilia W. Lo, Cécile Masson, Molly Schwartz, Rajae El Malti, Loïc de Pontual, G Jimenez, George C. Gabriel, Nikolai Klena, Hui Liu, Hisato Yagi, Candice N. Baker, Sylvie Di Filippo, Christopher T. Gordon, Damien Bonnet, Michael Tsang, Patric Schoen, Myriam Oufadem, Isabelle Thiffault, Laurie D. Smith, Linda D. Cooley, Anne Moreau de Bellaing, Patrick Nitschké, Patrice Bouvagnet, Emily G. Farrow, Anne Guimier, Aaron Noll, Fanny Bajolle, Carol J Saunders, Stephen F. Kingsmore, Kevin A. Peterson, Neil A. Miller, Jean-François Deleuze, Stanislas Lyonnet, Stephen A. Murray, Jeanne Amiel, and Christine Bole-Feysot
- Subjects
Heart Defects, Congenital ,Male ,medicine.medical_specialty ,Embryo, Nonmammalian ,Genes, Recessive ,In situ hybridization ,Heterotaxy Syndrome ,Article ,Mice ,Matrix Metalloproteinases, Secreted ,Genetics ,medicine ,Animals ,Humans ,Point Mutation ,Zebrafish ,In Situ Hybridization ,Body Patterning ,Family Health ,biology ,MMP21 ,Point mutation ,Embryogenesis ,Gene Expression Regulation, Developmental ,Heart ,Sequence Analysis, DNA ,Zebrafish Proteins ,biology.organism_classification ,Pedigree ,Laterality ,Vertebrates ,Medical genetics ,Female ,Heterotaxy - Abstract
Heterotaxy results from a failure to establish normal left-right asymmetry early in embryonic development. By whole-exome sequencing, whole-genome sequencing and high-throughput cohort resequencing, we identified recessive mutations in MMP21 (encoding matrix metallopeptidase 21) in nine index cases with heterotaxy. In addition, Mmp21-mutant mice and mmp21-morphant zebrafish displayed heterotaxy and abnormal cardiac looping, respectively, suggesting a new role for extracellular matrix remodeling in the establishment of laterality in vertebrates.
- Published
- 2015
26. Human Genetics of d-Transposition of the Great Arteries
- Author
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Patrice Bouvagnet and Anne Moreau de Bellaing
- Subjects
Genetics ,congenital, hereditary, and neonatal diseases and abnormalities ,Nephronophthisis ,Great arteries ,medicine ,Context (language use) ,Copy-number variation ,Biology ,medicine.disease ,X chromosome ,Exome sequencing ,Human genetics ,GDF1 - Abstract
Dextro-transposition of the great arteries (d-TGA) is one of the rare congenital heart diseases (CHD) which benefits from early neonatal diagnosis because d-TGA requires rapid postnatal catheter procedure. In that respect, detecting parental genetic predisposing factors would contribute to focusing prenatal echographical attention to the early detection of d-TGA cases. A high male to female ratio and a high recurrence risk of d-TGA in the context of heterotaxy suggest the impact of genetic factors although familial cases of d-TGA are exceptional. Since the late 1990s, a growing list of genes and chromosomal regions was associated with d-TGA among which the ZIC3 gene. Although this gene is located on the X chromosome, ZIC3 (Zic family member 3) does not explain the male preponderance in d-TGA. d-TGA causal genes are involved in many different cellular pathways and can be provisionally sorted in two groups: those which disrupt the function of the embryonic node cilia and those which are downstream of this major embryological process of lateralization. Many more genes or gene factors remain to be discovered in d-TGA and related CHD because only a small percentage of d-TGA is yet genetically resolved.
- Published
- 2016
27. Systemic atrioventricular valve replacement by mechanical prosthesis in children: Evolution in practice and predictors of long-term outcome
- Author
-
Anne Moreau de Bellaing, Damien Bonnet, Pascal Vouhé, Fanny Bajolle, and A. Haydar
- Subjects
medicine.medical_specialty ,Heart block ,business.industry ,medicine.medical_treatment ,Prosthesis Implantation ,medicine.disease ,Prosthesis ,Thrombosis ,Surgery ,Atrioventricular valve replacement ,medicine ,Atrioventricular canal ,Endocarditis ,Cardiology and Cardiovascular Medicine ,business ,Stroke - Abstract
Introduction Systemic atrioventricular mechanical valve replacement (SAVR) in children is challenging particularly in the youngest because of poor long-term outcomes related to the fixed size of the prosthesis and the anticoagulation treatment. Methods We reviewed the clinical and surgical records of 85 children who underwent SAVR at our institution between 2000 and 2017. The median age and the median weight at first operation were respectively 3.1 years (range: 1 month to 17 y) and 11.4 kg (range: 2.5 to 68 kg). Twenty-six patients (31%) were Results Global mortality was 18%. One-year, five-year and ten-year patient survival was respectively 87%, 82% and 78%. No significant predictive factor was associated with operative mortality. Among survivors, the 10-year freedom from reoperation was 74%. Complications after SAVR included heart block requiring pacemaker (13%) with a higher risk in case of atrioventricular canal (P = 0.004), bleeding (7%), prosthesis thrombosis (3.5%), stroke (2%) and endocarditis (5%). By multivariate age-adjusted analysis, the surgical strategies were the most important contributors to the long-term outcome. While undergoing a prosthesis implantation in supra-annular position was at high risk of late complications (OR = 1.6, P = 0.017), using an inversed aortic prosthesis prevented them (OR = −2.3, P = 0.004). Conclusions SAVR replacement remains a challenging procedure with high mortality but limited mortality related to anticoagulation. Modifications of the operative technics are one of the major causes of better long-term outcome.
- Published
- 2018
28. Functional Benefits of Bilateral Emphysema Reduction Surgery in an Adolescent
- Author
-
Anne Moreau de Bellaing, Marc Filaire, André Labbé, Valérie Julian, Ruddy Richard, Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Pulmonary disease ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,030212 general & internal medicine ,Respiratory system ,Pneumonectomy ,Dynamic hyperinflation ,ComputingMilieux_MISCELLANEOUS ,Reduction (orthopedic surgery) ,Postoperative Care ,Mechanical ventilation ,Respiratory Distress Syndrome, Newborn ,business.industry ,Respiration, Artificial ,Respiratory Function Tests ,Surgery ,Treatment Outcome ,030228 respiratory system ,Respiratory failure ,Walk test ,Disease Progression ,Quality of Life ,Female ,Maximal exercise ,Lung Volume Measurements ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Acquired emphysema is a rare pathology in pediatrics. We report the case of a patient born at term with a neonatal respiratory distress, which had required mechanical ventilation. She developed gradually chronic obstructive pulmonary disease with severe emphysematous lesions, respiratory failure and functional impairments. Bilateral emphysema resection, performed at 16 years old, allowed major functional benefits at rest and during exercise. We present the results of respiratory functional evaluations, walk tests and maximal exercise tests (including measure of dynamic hyperinflation) before and after surgery, which highlights that surgery is a successful option in the treatment of compressive emphysema in childhood.
- Published
- 2016
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