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

被引：2

作者：

McGinn, Daniel E. ^{[1
,2
]}

Crowley, T. Blaine ^{[1
]}

Heung, Tracy ^{[3
,4
]}

Oanh Tran ^{[1
]}

Moss, Edward ^{[1
]}

Zackai, Elaine H. ^{[1
,2
]}

Emanuel, Beverly S. ^{[1
,2
]}

Chow, Eva W. C. ^{[3
,5
]}

Morrow, Bernice E. ^{[6
]}

Swillen, Ann ^{[7
]}

Bassett, Anne S. ^{[3
,4
,5
,8
,9
]}

McDonald-McGinn, Donna M. ^{[1
,2
]}

机构：

[1] Childrens Hosp Philadelphia, 22q & You Ctr, Clin Genet Ctr, Div Human Genet, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Ctr Addict & Mental Hlth, Clin Genet Res Program, Toronto, ON M5G 2C4, Canada

[4] Univ Hlth Network, Dalglish Family 22q Clin, Toronto, ON M5G 2C4, Canada

[5] Univ Toronto, Dept Psychiat, Toronto, ON M5G 2C4, Canada

[6] Albert Einstein Coll Med, Bronx, NY 10461 USA

[7] Univ Leuven KU Leuven, Univ Hosp Leuven, Ctr Human Genet, Dept Human Genet, B-3000 Leuven, Belgium

[8] Toronto Gen Hosp, Res Inst, Toronto, ON M5G 2C4, Canada

[9] Campbell Family Mental Hlth Res Inst, Toronto, ON M5G 2C4, Canada

来源：

GENES | 2022年 / 13卷 / 10期

基金：

加拿大健康研究院;

关键词：

chromosome; 22q; deletion; DiGeorge; FSIQ; familial; parent-of-origin; intellect; de novo; PSYCHOSOCIAL ADJUSTMENT; CHILDREN;

D O I：

10.3390/genes13101800

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 similar to 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.

引用

页数：7