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TRAPPC9 deficiency’s implication in “secondary” autism spectrum disorders

Published online by Cambridge University Press:  19 July 2023

F. Majdoub ,
A. Bouzid ,
A. Souissi ,
I. Boujelbene ,
W. Bouchaala ,
F. Kamoun ,
M. Ben said ,
C. Triki ,
S. Masmoudi  and
I. Ben Ayed
F. Majdoub*
Affiliation:
Medical Genetics Department, University Hedi Chaker Hospital of Sfax, Tunisia., Medical school of Sfax, Tunisia
A. Bouzid
Affiliation:
Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax, University of Sfax
A. Souissi
Affiliation:
Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax, University of Sfax
I. Boujelbene
Affiliation:
Medical Genetics Department, University Hedi Chaker Hospital of Sfax, Tunisia., Medical school of Sfax, Tunisia
W. Bouchaala
Affiliation:
Child Neurology Department, University Hedi Chaker Hospital of Sfax, Medical school of Sfax, Tunisia, Sfax, Tunisia
F. Kamoun
Affiliation:
Child Neurology Department, University Hedi Chaker Hospital of Sfax, Medical school of Sfax, Tunisia, Sfax, Tunisia
M. Ben said
Affiliation:
Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax, University of Sfax
C. Triki
Affiliation:
Child Neurology Department, University Hedi Chaker Hospital of Sfax, Medical school of Sfax, Tunisia, Sfax, Tunisia
S. Masmoudi
Affiliation:
Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax, University of Sfax
I. Ben Ayed
Affiliation:
Medical Genetics Department, University Hedi Chaker Hospital of Sfax, Tunisia., Medical school of Sfax, Tunisia
*
*Corresponding author.

Abstract

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Introduction

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes. Multiple intellectual disability (ID) susceptibility genes have been identified in ASDs to date. The trafficking protein particle complex subunit 9 TRAPPC9 (OMIM#611966) in an autosomal recessive intellectual disability (ID) gene associated with not fully penetrant phenotype combining secondary microcephaly, dysmorphic facial features, obesity, autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD).

Objectives

The aim of this study is to consider TRAPPC9 deficiency in autosomal recessive ID with ASD.

Methods

We present the observation of two siblings, born to Tunisian consanguineous and healthy parents, followed up for syndromic intellectual disability (ID) associated ASD and microcephaly. A clinical exome sequencing was performed to one child using a Trusight One kit of Illumina. We used sanger sequencing to validate the suspected variant for the other child and to specify the parental segregation.

Results

A homozygous pathogenic variant in the TRAPPC9 (NM_001160372.4) gene, c.1414C > T (p. Arg472Ter) were identified in one child. Sanger sequencing confirmed the homozygosity profile of this variant for the other child while the parents were both heterozygous carriers.

Conclusions

Repetitive behaviours, especially hand-flapping, were the mean ASD feature in our patients. The current variant is known in the Tunisian population. It is described to lead to the creation of a premature stop codon and a truncating protein causing a TRAPPC9 deficiency. The impairing neuronal NFkB signalling due to TRAPPC9 deficiency has been suggested to be implicated in ASD. Due to the profound ID seen in both patients, we suggest the classification of ASD related to TRAPPC9 deficiency as “secondary” rather than “primary”.

Our results support the implication of TRAPPC9 in secondary ASD and shed the light on the possibility of screening p. Arg472Ter in Tunisian patients with this form of ASD as it is a recurrent mutation in the Tunisian population.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 66 , Special Issue S1: Abstracts of the 31st European Congress of Psychiatry , March 2023 , pp. S513
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 (https://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), 2023. Published by Cambridge University Press on behalf of the European Psychiatric Association
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