Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct 5;13(10):1800.
doi: 10.3390/genes13101800.

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

Daniel E McGinn  1   2 , T Blaine Crowley  1 , Tracy Heung  3   4 , Oanh Tran  1 , Edward Moss  1 , Elaine H Zackai  1   2 , Beverly S Emanuel  1   2 , Eva W C Chow  3   5 , Bernice E Morrow  6 , Ann Swillen  7 , Anne S Bassett  3   4   5   8 , Donna M McDonald-McGinn  1   2
Affiliations

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

Daniel E McGinn et al. Genes (Basel). .

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.

Keywords: 22q; DiGeorge; FSIQ; chromosome; de novo; deletion; familial; intellect; parent-of-origin.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Major effect of the chromosome 22q11.2 deletion on IQ (from average 100), with further leftward shift for inherited 22q11.2 deletions compared with de novo 22q11.2 deletions.
Figure 2
Figure 2
Individuals with inherited deletions of maternal origin were found to have a lower median FSIQ than those of paternal origin.
See this image and copyright information in PMC

References

    1. Blagojevic C., Heung T., Theriault M., Tomita-Mitchell A., Chakraborty P., Kernohan K., Bulman D.E., Bassett A.S. Estimate of the Contemporary Live-Birth Prevalence of Recurrent 22q11.2 Deletions: A Cross-Sectional Analysis from Population-Based Newborn Screening. CMAJ Open. 2021;9:E802–E809. doi: 10.9778/cmajo.20200294. - DOI - PMC - PubMed
    1. Grati F.R., Molina Gomes D., Ferreira J.C.P.B., Dupont C., Alesi V., Gouas L., Horelli-Kuitunen N., Choy K.W., García-Herrero S., de la Vega A.G., et al. Prevalence of Recurrent Pathogenic Microdeletions and Microduplications in over 9500 Pregnancies. Prenat Diagn. 2015;35:801–809. doi: 10.1002/pd.4613. - DOI - PubMed
    1. McDonald-McGinn D.M., Sullivan K.E., Marino B., Philip N., Swillen A., Vorstman J.A.S., Zackai E.H., Emanuel B.S., Vermeesch J.R., Morrow B.E., et al. 22q11.2 Deletion Syndrome. Nat. Rev. Dis. Prim. 2015;1:15071. doi: 10.1038/nrdp.2015.71. - DOI - PMC - PubMed
    1. Campbell I.M., Sheppard S.E., Crowley T.B., McGinn D.E., Bailey A., McGinn M.J., Unolt M., Homans J.F., Chen E.Y., Salmons H.I., et al. What Is New with 22q? An Update from the 22q and You Center at the Children’s Hospital of Philadelphia. Am. J. Med. Genet A. 2018;176:2058–2069. doi: 10.1002/ajmg.a.40637. - DOI - PMC - PubMed
    1. McDonald-McGinn D.M., Tonnesen M.K., Laufer-Cahana A., Finucane B., Driscoll D.A., Emanuel B.S., Zackai E.H. Phenotype of the 22q11.2 Deletion in Individuals Identified through an Affected Relative: Cast a Wide FISHing Net! Genet Med. 2001;3:23–29. doi: 10.1097/00125817-200101000-00006. - DOI - PubMed

Publication types

LinkOut - more resources