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Identification of candidate genes of intellectual disability by single-gene deletions/amplifications mapping using chromosomal microarray analysis

Published online by Cambridge University Press:  01 September 2022

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

Disease-causing deletions/amplifications may include a single gene, several exons or single/part of exon, contributing to detection of novel pathogenic genes. The localization of single-gene deletion/amplification within the gene can affect its clinical manifestation.

Objectives

Improvement of diagnosis of intellectual disability.

Methods

aCGH with 60K Agilent microarrays, qPCR.

Results

Among 1099 patients with intellectual disability potentially pathogenic single-gene deletions/amplifications were detected in 51 individuals (5%). qPCR was used to verify aberrations in 21 patients (41%). Ten mutations were of maternal origin, four - paternal, two - de novo, another two were confirmed without analysis of parents, and three could not be confirmed. Single-gene aberrations involving the AGBL4 (exon 2), ASMT (exon 9), CYP2C18 (whole gene), DDX10 (promoter, exons 1-13), GYPA (whole gene), LIG4 (exon 1), LSAMP (intron 1), PSD3 (promoter, exons 1-11), SNTB1 (intron 1), SPOCK3 (exons 6-12), STAG2 (exons 7-34), SYT10 (promoter, exons 1-2), TCAF2 (exon 8), TMPRSS15 (promoter, exons 1-12), and ZDHHC7 (promoter, exons 1-4) genes were described by us for the first time. Deletion or amplification of several exons within a gene can affect transcription as point mutation does, while the copy number change of a whole gene can lead to an abnormal amount of the protein.

Conclusions

Fifteen novel genes potentially responsible for mental health were identified. In most of them aberrations were partial deletions/duplications. Most of abnormalities were inherited from healthy parents indicating the possible presence of a point mutation on the second allele or some modifying factors. This study was supported by the Russian Science Foundation, grant 21-65-00017.

Disclosure

No significant relationships.

Keywords

intellectual disabilitySingle-gene deletionSingle-gene amplification
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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