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

International 22q11.2 Brain and Behavior Consortium

Research output: Contribution to journalArticle

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 languageEnglish
JournalAmerican Journal of Medical Genetics, Part A
DOIs
Publication statusE-pub ahead of print - Oct 5 2018

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DiGeorge Syndrome
Base Pairing
Genomic Segmental Duplications
Haploinsufficiency
Homologous Recombination
Gene Deletion
Meiosis
Heart Diseases
Population
Genes

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Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects. / International 22q11.2 Brain and Behavior Consortium.

In: American Journal of Medical Genetics, Part A, 05.10.2018.

Research output: Contribution to journalArticle

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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.",
author = "{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}",
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AU - International 22q11.2 Brain and Behavior Consortium

AU - Zhao, Yingjie

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AU - Fiksinski, Ania

AU - Breetvelt, Elemi

AU - McDonald-McGinn, Donna M

AU - Crowley, Terrence B

AU - Diacou, Alexander

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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

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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

N1 - © 2018 Wiley Periodicals, Inc.

PY - 2018/10/5

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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.

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DO - 10.1002/ajmg.a.40359

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JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

ER -