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

Yingjie Zhao, Tingwei Guo, Ania Fiksinski, Elemi Breetvelt, Donna M. McDonald-McGinn, Terrence B. Crowley, Alexander Diacou, Maude Schneider, Stephan Eliez, Ann Swillen, Jeroen Breckpot, Joris Vermeesch, Eva W. C. Chow, Doron Gothelf, Sasja Duijff, Rens Evers, Therese A. van Amelsvoort, Marianne van den Bree, Michael Owen, Maria NiarchouCarrie E. Bearden, Claudia Ornstein, Maria Pontillo, Antonino Buzzanca, Stefano Vicari, Marco Armando, Kieran C. Murphy, Clodagh Murphy, Sixto Garcia-Minaur, Nicole Philip, Linda Campbell, Jaume Morey-Canellas, Jasna Raventos, Jordi Rosell, Damian Heine-Suner, Robert J. Shprintzen, Raquel E. Gur, Elaine Zackai, Beverly S. Emanuel, Tao Wang, Wendy R. Kates, Anne S. Bassett, Jacob A. S. Vorstman, Bernice E. Morrow*, Int Brain Behavior Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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
Pages (from-to)2172-2181
Number of pages10
JournalAmerican Journal of Medical Genetics Part A
Issue number10
Publication statusPublished - 1 Oct 2018


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


Dive into the research topics of 'Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects'. Together they form a unique fingerprint.

Cite this