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

on behalf of the International 22q11.2 Brain and Behavior Consortium

Research output: Contribution to journalArticle

1 Citation (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 languageEnglish (US)
Pages (from-to)2172-2181
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Volume176
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

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

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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

In: American Journal of Medical Genetics, Part A, Vol. 176, No. 10, 01.10.2018, p. 2172-2181.

Research output: Contribution to journalArticle

on behalf of the International 22q11.2 Brain and Behavior Consortium. / Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects. In: American Journal of Medical Genetics, Part A. 2018 ; Vol. 176, No. 10. pp. 2172-2181.
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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.",
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AU - Zhao, Yingjie

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AU - Fiksinski, Ania

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AU - McDonald-McGinn, Donna M.

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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

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AU - Bassett, Anne S.

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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.

KW - 22q11.2 deletion syndrome

KW - deletion size

KW - intellectual disability

KW - IQ

KW - low copy repeat

KW - segmental duplication

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