Influence of Parent-of-Origin on Intellectual Outcomes in the Chromosome 22q11.2 Deletion Syndrome

Daniel E. McGinn, T. Blaine Crowley, Tracy Heung, Oanh Tran, Edward Moss, Elaine H. Zackai, Beverly S. Emanuel, Eva W.C. Chow, Bernice E. Morrow, Ann Swillen, Anne S. Bassett, Donna M. McDonald-McGinn

Research output: Contribution to journalArticlepeer-review

Abstract

Learning and intellectual disabilities are hallmark features of 22q11.2 deletion syndrome. Data are limited, however, regarding influences on full-scale IQ (FSIQ). Here, we investigated possible 22q11.2 deletion parent-of-origin effects. In 535 individuals, we compared FSIQ (≥50), 481 with de novo and 54 with inherited 22q11.2 deletions. In the subsets with data available, we examined parent-of-origin effects on FSIQ. We used linear regression models to account for covariates. Median FSIQ was significantly higher in de novo vs. inherited deletions (77; range 50–116 vs. 67; range 50–96, p < 0.0001). Results remained significant using a regression model accounting for age at IQ testing, sex and cohort site. No significant parent-of-origin differences in FSIQ were observed for de novo deletions (n = 81, 63.0% maternal; p = 0.6882). However, median FSIQ was significantly lower in maternally than in paternally inherited familial deletions (65, range 50–86 vs. 71.5, range 58–96, respectively, p = 0.0350), with the regression model indicating an ~8 point decrement in FSIQ for this variable (p = 0.0061). FSIQ is higher on average in de novo than in inherited 22q11.2 deletions, regardless of parental origin. However, parent-of-origin appears relevant in inherited deletions. The results have potential clinical implications with further research needed to delineate possible actionable mechanisms.

Original languageEnglish (US)
Article number1800
JournalGenes
Volume13
Issue number10
DOIs
StatePublished - Oct 2022

Keywords

  • 22q
  • DiGeorge
  • FSIQ
  • chromosome
  • de novo
  • deletion
  • familial
  • intellect
  • parent-of-origin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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