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Concomitant CNVs in healthy carriers with 7q31.1 microdeletions may suppress intellectual disability and autism spectrum disorders phenotype

Published online by Cambridge University Press:  01 September 2022

E. Belyaeva ,
A. Kashevarova ,
G. Drozdov ,
D. Fedotov  and
I. Lebedev
E. Belyaeva*
Affiliation:
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Laboratory Of Ontogenetics, Tomsk, Russian Federation
A. Kashevarova
Affiliation:
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Laboratory Of Ontogenetics, Tomsk, Russian Federation
G. Drozdov
Affiliation:
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Laboratory Of Ontogenetics, Tomsk, Russian Federation
D. Fedotov
Affiliation:
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Laboratory Of Ontogenetics, Tomsk, Russian Federation
I. Lebedev
Affiliation:
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Laboratory Of Ontogenetics, Tomsk, Russian Federation
*
*Corresponding author.

Abstract

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Introduction

About 66% of chromosomal microdeletions and microduplications associated with pathological conditions are inherited [Smajlagić D. et al., 2021]. The mechanisms of incomplete penetrance and variable expressivity of CNV are not fully understood. The presence of concomitant CNVs in the genome of healthy parents may have a modifying effect.

Objectives

Identification of additional CNVs in healthy carriers with 7q31.1 microdeletions.

Methods

CNVs were revealed by Agilent Technologies 60K microarray and confirmed by qPCR.

Results

We examined 3 families with inherited 7q31.1 microdeletions affecting only the IMMP2L gene, which is associated with intellectual disability, developmental delay and autism spectrum disorders. Family 1: Proband has intellectual disability, developmental delay, sensorimotor alalia. Microdeletion was inherited from the father, and a healthy sibling is also a carrier of rearrangement. In sibs, additional CNVs were identified: arr[hg19]: 4q31.21(144722583_144939143)×3; 9p12p11.2(43588066_43836428)×3; 16p11.2(32066967_33773163)×1; and 17q21.31(44199517_44577208)×3. Family 2: Proband suffers from development delay, speech disorder and autism. Microdeletion was of paternal origin. The father additionally demonstrated microduplication 16p11.2p11.1(33967926-35204414)×3. Family 3: Proband was diagnosed with development delay and cerebral palsy. The mother is a carrier of a similar 7q31.1 microdeletion; two concomitant CNVs were identified in her karyotype: 9p13.1(39176840_40614884)×3; and 16p11.2p11.1(32833891_35204414)×3. Thus, healthy parents in 3 families have CNV in a common region 16p11.2, which contains the TP53TG3 gene. It is important that TP53TG3 expression is associated with epistatic CNV-CNV interactions [Sun, Kardia 2010].

Conclusions

Multiple CNVs in apparently healthy carriers of IMMP2L microdeltions may suppress disease phenotype due to the epistatic CNV-CNV interaction. This study was supported by Russian Science Foundation, grant no. 21-75-00112.

Disclosure

No significant relationships.

Keywords

intellectual disabilityIMMP2LCNV
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S382
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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