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Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes

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  • Maria Delio
  • Tingwei Guo
  • Donna M McDonald-McGinn
  • Elaine Zackai
  • Sean Herman
  • Mark Kaminetzky
  • Anne Marie Higgins
  • Karlene Coleman
  • Carolyn Chow
  • Maria Jalbrzikowski
  • Maria Jarlbrzkowski
  • Carrie E Bearden
  • Alice Bailey
  • Anders Vangkilde
  • Line Olsen
  • Charlotte Olesen
  • Flemming Skovby
  • Thomas M Werge
  • Ludivine Templin
  • Tiffany Busa
  • Nicole Philip
  • Ann Swillen
  • Joris R Vermeesch
  • Koen Devriendt
  • Maude Schneider
  • Sophie Dahoun
  • Stephan Eliez
  • Kelly Schoch
  • Stephen R Hooper
  • Vandana Shashi
  • Joy Samanich
  • Robert Marion
  • Therese van Amelsvoort
  • Erik Boot
  • Petra Klaassen
  • Sasja N Duijff
  • Jacob Vorstman
  • Tracy Yuen
  • Candice Silversides
  • Eva Chow
  • Anne Bassett
  • Amos Frisch
  • Abraham Weizman
  • Doron Gothelf
  • Maria Niarchou
  • Marianne van den Bree
  • Michael J Owen
  • Damian Heine Suñer
  • Jordi Rosell Andreo
  • Marco Armando
  • Stefano Vicari
  • Maria Cristina Digilio
  • Adam Auton
  • Wendy R Kates
  • Tao Wang
  • Robert J Shprintzen
  • Beverly S Emanuel
  • Bernice E Morrow
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Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.
Original languageEnglish
JournalAmerican Journal of Human Genetics
Volume92
Issue number3
Pages (from-to)439-47
Number of pages9
DOIs
Publication statusPublished - 7 Mar 2013

Bibliographical note

Maria Delio1, Tingwei Guo1, Donna M. McDonald-McGinn2, 3, Elaine Zackai2, 3, 4, Sean Herman1, Mark Kaminetzky1, Anne Marie Higgins5, Karlene Coleman6, 7, Carolyn Chow8, Maria Jarlbrzkowski8, Carrie E. Bearden8, Alice Bailey2, 3, Anders Vangkilde9, Line Olsen9, Charlotte Olesen10, Flemming Skovby11, Thomas M. Werge9, Ludivine Templin11, Tiffany Busa11, Nicole Philip12, Ann Swillen13, Joris R. Vermeesch13, Koen Devriendt13, Maude Schneider14, Sophie Dahoun14, Stephan Eliez14, Kelly Schoch15, Stephen R. Hooper16, 17, Vandana Shashi15, Joy Samanich18, Robert Marion18, Therese van Amelsvoort19, Erik Boot20, Petra Klaassen21, Sasja N. Duijff21, Jacob Vorstman22, Tracy Yuen23, Candice Silversides23, Eva Chow23, Anne Bassett23, Amos Frisch24, Abraham Weizman25, Doron Gothelf25, 26, Maria Niarchou27, Marianne van den Bree27, Michael J. Owen27, Damian Heine Suñer28, Jordi Rosell Andreo28, Marco Armando29, Stefano Vicari29, Maria Cristina Digilio30, Adam Auton31, Wendy R. Kates32, Tao Wang33, Robert J. Shprintzen5, Beverly S. Emanuel2, 3, 4 and Bernice E. Morrow1, 34, Go To Corresponding Author,

1 Departments of Genetics, Pediatrics, and Obstetrics & Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
3 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
4 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5 The Virtual Center for Velo-Cardio-Facial Syndrome, Manlius, NY 13104, USA
6 Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
7 Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA 30322, USA
8 Department of Psychiatry and Biobehavioral Sciences and Department of Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA
9 Institute of Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Copenhagen 4000, Denmark
10 Department of Pediatrics, Aarhus University Hospital, Aarhus 8000, Denmark
11 Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen 2100, Denmark
12 Hôpital de la Timone, Assistance Publique – Hôpitaux de Marseille, Marseille 13005, France
13 Center for Human Genetics, University Hospital Gasthuisberg, University of Leuven, Leuven 03000, Belgium
14 Office Médico-Pédagogique Research Unit, Department of Psychiatry, University of Geneva School of Medicine, Geneva 1211, Switzerland
15 Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27705, USA
16 Department of Psychiatry and The Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA
17 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA
18 Department of Pediatrics, Montefiore Medical Center, Bronx, NY 10461, USA
19 Department of Psychiatry and Psychology, University of Maastricht, Maastricht 6211, the Netherlands
20 Department of Psychiatry, Academic Medical Centre, Amsterdam 1100, the Netherlands
21 Department of Pediatric Psychology, University Medical Center Utrecht, Utrecht 3584, the Netherlands
22 Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht 3584, the Netherlands
23 Center for Addiction and Mental Health, University of Toronto, Toronto, ON M5T 1R8, Canada
24 The Felsenstein Medical Research Center, Petah Tikva 49100, Israel
25 The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
26 The Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel
27 Medical Research Council Centre for Neuropsychiatric Genetics & Genomics and the Neuroscience & Mental Health Research Institute, Cardiff University, Cardiff CF14 4XN, UK
28 Laboratory of Molecular Genetics, Department of Genetics, University Hospital Son Espases, Palma de Mallorca 07020, Spain
29 Child Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome 00165, Italy
30 Medical Genetic Unit, Department of Pediatrics, Bambino Gesù Children’s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome 00165, Italy
31 Division of Computational Genetics, Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA

    Research areas

  • Adult, Chromosome Deletion, Chromosomes, Human, Pair 22, DiGeorge Syndrome, Female, Genetic Predisposition to Disease, Genotype, Humans, Male

ID: 42634229