Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects

the International 22q11.2 Brain and Behavior Consortium

doi:10.1002/ajmg.a.40359

Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects

the International 22q11.2 Brain and Behavior Consortium

Physics

Department of Genetic Medicine and Development
University of Geneva
Albert Einstein College of Medicine
University Medical Centre Utrecht
University of Toronto
Toronto General Hospital
Centre for Addiction and Mental Health
University of Pennsylvania Perelman School of Medicine
Research Institute
KU Leuven
University of Toronto
Tel Aviv University
Sheba Medical Center
Maastricht University Medical Centre
Cardiff University
University of California
Hospital Clinico Universidad de Chile
Children Hospital Bambino Gesu
Sapienza University of Rome
Royal College of Surgeons in Ireland
King's College London
La Paz University Hospital
Aix-Marseille University
University of Newcastle
Hospital Son Dureta
The Virtual Center for Velo-Cardio-Facial Syndrome and Related Disorders
University of Pennsylvania
SUNY Upstate Medical University
State University of New York
Hospital General Universitario Gregorio Marañón
Sapienza University
Hospital General Universitario Gregorio Marañón
Aix-Marseille Université
Emory University and Children's Healthcare of Atlanta
Emory University School of Medicine
Cincinnati Children's Hospital Medical Center
Duke University
University of North Carolina
University of Geneva
Complutense University
Chile Sociedad Chilena de Desarrollo Emocional
Duke University School of Medicine
University of California Davis
University of California Davis
Children's Hospital of Wisconsin

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

37 Citations (Scopus)

Abstract

The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p =.002), verbal IQ was decreased by 8.17 points (p =.0002) and performance IQ was decreased by 4.03 points (p =.028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort.

Original language	English
Pages (from-to)	2172-2181
Number of pages	10
Journal	American Journal of Medical Genetics, Part A
Volume	176
Issue number	10
DOIs	https://doi.org/10.1002/ajmg.a.40359
Publication status	Published - 1 Oct 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

22q11.2 deletion syndrome
deletion size
intellectual disability
IQ
low copy repeat
segmental duplication

Access to Document

10.1002/ajmg.a.40359

Cite this

@article{aeffd3cbc4744302bb98c554a0ad7fde,

title = "Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects",

abstract = "The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p =.002), verbal IQ was decreased by 8.17 points (p =.0002) and performance IQ was decreased by 4.03 points (p =.028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort.",

keywords = "22q11.2 deletion syndrome, deletion size, intellectual disability, IQ, low copy repeat, segmental duplication",

author = "\{the International 22q11.2 Brain and Behavior Consortium\} and Yingjie Zhao and Tingwei Guo and Ania Fiksinski and Elemi Breetvelt and McDonald-McGinn, \{Donna M.\} and Crowley, \{Terrence B.\} and Alexander Diacou and Maude Schneider and Stephan Eliez and Ann Swillen and Jeroen Breckpot and Joris Vermeesch and Chow, \{Eva W.C.\} and Doron Gothelf and Sasja Duijff and Rens Evers and \{van Amelsvoort\}, \{Th{\'e}r{\`e}se A.\} and \{van den Bree\}, Marianne and Michael Owen and Maria Niarchou and Bearden, \{Carrie E.\} and Claudia Ornstein and Maria Pontillo and Antonino Buzzanca and Stefano Vicari and Marco Armando and Murphy, \{Kieran C.\} and Clodagh Murphy and Sixto Garcia-Minaur and Nicole Philip and Linda Campbell and Jaume Morey-Ca{\~n}ellas and Jasna Raventos and Jordi Rosell and Damian Heine-Suner and Shprintzen, \{Robert J.\} and Gur, \{Raquel E.\} and Elaine Zackai and Emanuel, \{Beverly S.\} and Tao Wang and Kates, \{Wendy R.\} and Bassett, \{Anne S.\} and Vorstman, \{Jacob A.S.\} and Morrow, \{Bernice E.\} and Antonarakis, \{Stylianos E.\} and Kevin Antshel and Celso Arango and Massimo Biondi and Anna Blonska and Erik Boot and Marta Bravo-Sanchez and Tiffany Busa and Nancy Butcher and Monica Calkins and Miri Carmel and Samuel Chawner and Karlene Coleman and Joseph Cubells and David Cutler and Bruno Dallapiccola and Wolfram Demaerel and Koen Devriendt and \{Di Fabio\}, Fabio and Digilio, \{Maria Cristina\} and Michael Epstein and \{Fernandez Garcia-Moya\}, Luis and David Fraguas and Wanda Fremont and Rosemarie Fritsch and Aaron Golden and Matthew Hestand and Tracy Heung and Stephen Hooper and Johnston, \{H. Richard\} and Leila Kushan-Wells and Alejandra Laorden-Nieto and Guido Lattanzi and Lin, \{Jhih Rong\} and Johanna Maeder and Bruno Marino and Marshall, \{Christian R.\} and Maria Mayoral and Kathryn McCabe and Daniel McGinn and Elena Michaelovsky and Edward Moss and Hayley Moss and Jennifer Mulle and Declan Murphy and Gabriela Repetto and Vandana Shashi and Tony Simon and Sunny Tang and Flora Tassone and Aoy Tomita-Mitchell and Marta Unolt and \{van Duin\}, \{Esther D.A.\} and Elfi Vergaelen and Cecilia Vial and Claudia Vingerhoets",

note = "Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",

year = "2018",

month = oct,

day = "1",

doi = "10.1002/ajmg.a.40359",

language = "English",

volume = "176",

pages = "2172--2181",

journal = "American Journal of Medical Genetics, Part A",

issn = "1552-4825",

publisher = "John Wiley and Sons Inc",

number = "10",

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TY - JOUR

T1 - Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects

AU - the International 22q11.2 Brain and Behavior Consortium

AU - Zhao, Yingjie

AU - Guo, Tingwei

AU - Fiksinski, Ania

AU - Breetvelt, Elemi

AU - McDonald-McGinn, Donna M.

AU - Crowley, Terrence B.

AU - Diacou, Alexander

AU - Schneider, Maude

AU - Eliez, Stephan

AU - Swillen, Ann

AU - Breckpot, Jeroen

AU - Vermeesch, Joris

AU - Chow, Eva W.C.

AU - Gothelf, Doron

AU - Duijff, Sasja

AU - Evers, Rens

AU - van Amelsvoort, Thérèse A.

AU - van den Bree, Marianne

AU - Owen, Michael

AU - Niarchou, Maria

AU - Bearden, Carrie E.

AU - Ornstein, Claudia

AU - Pontillo, Maria

AU - Buzzanca, Antonino

AU - Vicari, Stefano

AU - Armando, Marco

AU - Murphy, Kieran C.

AU - Murphy, Clodagh

AU - Garcia-Minaur, Sixto

AU - Philip, Nicole

AU - Campbell, Linda

AU - Morey-Cañellas, Jaume

AU - Raventos, Jasna

AU - Rosell, Jordi

AU - Heine-Suner, Damian

AU - Shprintzen, Robert J.

AU - Gur, Raquel E.

AU - Zackai, Elaine

AU - Emanuel, Beverly S.

AU - Wang, Tao

AU - Kates, Wendy R.

AU - Bassett, Anne S.

AU - Vorstman, Jacob A.S.

AU - Morrow, Bernice E.

AU - Antonarakis, Stylianos E.

AU - Antshel, Kevin

AU - Arango, Celso

AU - Biondi, Massimo

AU - Blonska, Anna

AU - Boot, Erik

AU - Bravo-Sanchez, Marta

AU - Busa, Tiffany

AU - Butcher, Nancy

AU - Calkins, Monica

AU - Carmel, Miri

AU - Chawner, Samuel

AU - Coleman, Karlene

AU - Cubells, Joseph

AU - Cutler, David

AU - Dallapiccola, Bruno

AU - Demaerel, Wolfram

AU - Devriendt, Koen

AU - Di Fabio, Fabio

AU - Digilio, Maria Cristina

AU - Epstein, Michael

AU - Fernandez Garcia-Moya, Luis

AU - Fraguas, David

AU - Fremont, Wanda

AU - Fritsch, Rosemarie

AU - Golden, Aaron

AU - Hestand, Matthew

AU - Heung , Tracy

AU - Hooper, Stephen

AU - Johnston, H. Richard

AU - Kushan-Wells, Leila

AU - Laorden-Nieto, Alejandra

AU - Lattanzi, Guido

AU - Lin, Jhih Rong

AU - Maeder, Johanna

AU - Marino, Bruno

AU - Marshall, Christian R.

AU - Mayoral, Maria

AU - McCabe, Kathryn

AU - McGinn, Daniel

AU - Michaelovsky, Elena

AU - Moss, Edward

AU - Moss, Hayley

AU - Mulle, Jennifer

AU - Murphy, Declan

AU - Repetto, Gabriela

AU - Shashi, Vandana

AU - Simon, Tony

AU - Tang, Sunny

AU - Tassone, Flora

AU - Tomita-Mitchell, Aoy

AU - Unolt, Marta

AU - van Duin, Esther D.A.

AU - Vergaelen, Elfi

AU - Vial, Cecilia

AU - Vingerhoets, Claudia

PY - 2018/10/1

Y1 - 2018/10/1

N2 - The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p =.002), verbal IQ was decreased by 8.17 points (p =.0002) and performance IQ was decreased by 4.03 points (p =.028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort.

AB - The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p =.002), verbal IQ was decreased by 8.17 points (p =.0002) and performance IQ was decreased by 4.03 points (p =.028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort.

KW - 22q11.2 deletion syndrome

KW - deletion size

KW - intellectual disability

KW - IQ

KW - low copy repeat

KW - segmental duplication

UR - https://www.scopus.com/pages/publications/85054522149

U2 - 10.1002/ajmg.a.40359

DO - 10.1002/ajmg.a.40359

M3 - Article

C2 - 30289625

AN - SCOPUS:85054522149

SN - 1552-4825

VL - 176

SP - 2172

EP - 2181

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

IS - 10

ER -

Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects

Abstract

UN SDGs

Keywords

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