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

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

Journal

Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097

Informations de publication

Date de publication:
05 10 2022
Historique:
received: 01 09 2022
revised: 21 09 2022
accepted: 29 09 2022
entrez: 27 10 2022
pubmed: 28 10 2022
medline: 29 10 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36292685
pii: genes13101800
doi: 10.3390/genes13101800
pmc: PMC9602066
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIMH NIH HHS
ID : U01 MH119738
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH101722
Pays : United States
Organisme : CIHR
ID : PJT-169161
Pays : Canada
Organisme : CIHR
ID : PJT-148924
Pays : Canada

Déclaration de conflit d'intérêts

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.

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Auteurs

Daniel E McGinn (DE)

The 22q and You Center, Clinical Genetics Center, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

T Blaine Crowley (TB)

The 22q and You Center, Clinical Genetics Center, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Tracy Heung (T)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5G 2C4, Canada.
The Dalglish Family 22q Clinic, University Health Network, Toronto, ON M5G 2C4, Canada.

Oanh Tran (O)

The 22q and You Center, Clinical Genetics Center, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Edward Moss (E)

The 22q and You Center, Clinical Genetics Center, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Elaine H Zackai (EH)

The 22q and You Center, Clinical Genetics Center, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Beverly S Emanuel (BS)

The 22q and You Center, Clinical Genetics Center, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Eva W C Chow (EWC)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5G 2C4, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON M5G 2C4, Canada.

Bernice E Morrow (BE)

Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Ann Swillen (A)

The Centre for Human Genetics, University Hospital of Leuven, Department of Human Genetics, University of Leuven (KU Leuven), 3000 Leuven, Belgium.

Anne S Bassett (AS)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON M5G 2C4, Canada.
The Dalglish Family 22q Clinic, University Health Network, Toronto, ON M5G 2C4, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON M5G 2C4, Canada.
Toronto General Hospital Research Institute, and Campbell Family Mental Health Research Institute, Toronto, ON M5G 2C4, Canada.

Donna M McDonald-McGinn (DM)

The 22q and You Center, Clinical Genetics Center, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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