Marguerite Hureaux1, Sarah Guterman2,3, Bérénice Hervé2,4, Marianne Till5, Sylvie Jaillard6, Sylvie Redon7, Myléne Valduga8, Charles Coutton9,10, Chantal Missirian11, Fabienne Prieur12, Brigitte Simon-Bouy13, Claire Beneteau14, Paul Kuentz15, Caroline Rooryck16, Nicolas Gruchy17, Nathalie Marle18, Morgane Plutino19, Lucie Tosca20, Celine Dupont21, Jacques Puechberty22, Caroline Schluth-Bolard5, Laurent Salomon23, Damien Sanlaville5, Valérie Malan1,24, François Vialard2,4. 1. Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, APHP, Paris, France. 2. EA7404-GIG, UFR des sciences de la Santé Simone Veil, UVSQ, Montigny le Bretonneux, France. 3. Service de Gynécologie Obstétrique, CHI de Poissy, St Germain, Poissy, France. 4. Unité de Cytogénétique, CHI de Poissy St Germain, Poissy, France. 5. Service de Génétique, Hospices civils de Lyon, Lyon, France. 6. Service de Cytogénétique, CHU de Rennes, Rennes, France. 7. Laboratoire de Cytogénétique, Cytologie et Biologie de la Reproduction, CHRU, Brest, France. 8. Service de Génétique, CHU Nancy-Brabois, Nancy, France. 9. Service de Génétique Chromosomique, Hôpital Couple-Enfant, CHU Grenoble Alpes, La Tronche, France. 10. Equipe GETI - IAB, INSERM U1209, Université Grenoble-Alpes, La Tronche, France. 11. Département de Génétique Médicale, CHU Timone Enfants, APHM, Marseille, France. 12. Service de Génétique Clinique Chromosomique Moléculaire, CHU Saint-Etienne, Saint-Etienne, France. 13. Génétique Constitutionnelle, Laboratoire de Biologie, Centre Hospitalier de Versailles, Le Chesnay, France. 14. Service de Génétique Médicale, CHU Nantes, Nantes, France. 15. Service de Génétique Biologique, CHRU Besançon, Besançon, France. 16. CHU de Bordeaux, Service de Génétique Médicale, Bordeaux, France. 17. Service de Génétique, CHU Caen, Caen, France. 18. Laboratoire de Génétique Chromosomique et Moléculaire, CHU Dijon, Dijon, France. 19. Service de Génétique, CHU Nice, Nice, France. 20. Service d'Histologie Embryologie Cytogénétique, Hôpital Antoine Béclère, Clamart, France. 21. Service de Cytogénétique, APHP Hôpital Robert Debré, Paris, France. 22. Service de Génétique, CHU Montpellier, Montpellier, France. 23. Service d'Obstétrique, Hôpital Necker-Enfants Malades, APHP, Paris, France. 24. Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
Abstract
OBJECTIVES: Congenital heart defects (CHDs) may be isolated or associated with other malformations. The use of chromosome microarray (CMA) can increase the genetic diagnostic yield for CHDs by between 4% and 10%. The objective of this study was to evaluate the value of CMA after the prenatal diagnosis of an isolated CHD. METHODS: In a retrospective, nationwide study performed in France, we collected data on all cases of isolated CHD that had been explored using CMAs in 2015. RESULTS: A total of 239 fetuses were included and 33 copy number variations (CNVs) were reported; 19 were considered to be pathogenic, six were variants of unknown significance, and eight were benign variants. The anomaly detection rate was 10.4% overall but ranged from 0% to 16.7% as a function of the isolated CHD in question. The known CNVs were 22q11.21 deletions (n = 10), 22q11.21 duplications (n = 2), 8p23 deletions (n = 2), an Alagille syndrome (n = 1), and a Kleefstra syndrome (n = 1). CONCLUSION: The additional diagnostic yield was clinically significant (3.1%), even when anomalies in the 22q11.21 region were not taken into account. Hence, patients with a suspected isolated CHD and a normal karyotype must be screened for chromosome anomalies other than 22q11.21 duplications and deletions.
OBJECTIVES:Congenital heart defects (CHDs) may be isolated or associated with other malformations. The use of chromosome microarray (CMA) can increase the genetic diagnostic yield for CHDs by between 4% and 10%. The objective of this study was to evaluate the value of CMA after the prenatal diagnosis of an isolated CHD. METHODS: In a retrospective, nationwide study performed in France, we collected data on all cases of isolated CHD that had been explored using CMAs in 2015. RESULTS: A total of 239 fetuses were included and 33 copy number variations (CNVs) were reported; 19 were considered to be pathogenic, six were variants of unknown significance, and eight were benign variants. The anomaly detection rate was 10.4% overall but ranged from 0% to 16.7% as a function of the isolated CHD in question. The known CNVs were 22q11.21 deletions (n = 10), 22q11.21 duplications (n = 2), 8p23 deletions (n = 2), an Alagille syndrome (n = 1), and a Kleefstra syndrome (n = 1). CONCLUSION: The additional diagnostic yield was clinically significant (3.1%), even when anomalies in the 22q11.21 region were not taken into account. Hence, patients with a suspected isolated CHD and a normal karyotype must be screened for chromosome anomalies other than 22q11.21 duplications and deletions.
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Back Sternick Eduardo; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong-Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti Mac Intyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Pablo Ochoa Juan; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: J Arrhythm Date: 2022-05-31
Authors: Arthur A M Wilde; Christopher Semsarian; Manlio F Márquez; Alireza Sepehri Shamloo; Michael J Ackerman; Euan A Ashley; Eduardo Back Sternick; Héctor Barajas-Martinez; Elijah R Behr; Connie R Bezzina; Jeroen Breckpot; Philippe Charron; Priya Chockalingam; Lia Crotti; Michael H Gollob; Steven Lubitz; Naomasa Makita; Seiko Ohno; Martín Ortiz-Genga; Luciana Sacilotto; Eric Schulze-Bahr; Wataru Shimizu; Nona Sotoodehnia; Rafik Tadros; James S Ware; David S Winlaw; Elizabeth S Kaufman; Takeshi Aiba; Andreas Bollmann; Jong Il Choi; Aarti Dalal; Francisco Darrieux; John Giudicessi; Mariana Guerchicoff; Kui Hong; Andrew D Krahn; Ciorsti MacIntyre; Judith A Mackall; Lluís Mont; Carlo Napolitano; Juan Pablo Ochoa; Petr Peichl; Alexandre C Pereira; Peter J Schwartz; Jon Skinner; Christoph Stellbrink; Jacob Tfelt-Hansen; Thomas Deneke Journal: Europace Date: 2022-09-01 Impact factor: 5.486
Authors: Katarzyna Kowalczyk; Magdalena Bartnik-Głaska; Marta Smyk; Izabela Plaskota; Joanna Bernaciak; Marta Kędzior; Barbara Wiśniowiecka-Kowalnik; Marta Deperas; Justyna Domaradzka; Alicja Łuszczek; Daria Dutkiewicz; Agata Kozar; Dominika Grad; Magdalena Niemiec; Kamila Ziemkiewicz; Róża Magdziak; Natalia Braun-Walicka; Artur Barczyk; Maciej Geremek; Jennifer Castañeda; Anna Kutkowska-Kaźmierczak; Paweł Własienko; Krystyna Jakubów-Durska; Marzena Dębska; Anna Kucińska-Chahwan; Szymon Kozłowski; Boyana Mikulska; Tadeusz Issat; Tomasz Roszkowski; Agnieszka Nawara-Baran; Agata Runge; Anna Jakubiuk-Tomaszuk; Anna Kruczek; Ewa Kostyk; Grzegorz Pietras; Janusz Limon; Jerzy Zwoliński; Karolina Ochman; Tomasz Szajner; Piotr Węgrzyn; Mirosław Wielgoś; Maria Sąsiadek; Ewa Obersztyn; Beata Anna Nowakowska Journal: Genes (Basel) Date: 2022-04-14 Impact factor: 4.141