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TRAPPC9 deficiency’s implication in “secondary” autism spectrum disorders
- F. Majdoub, A. Bouzid, A. Souissi, I. Boujelbene, W. Bouchaala, F. Kamoun, M. Ben said, C. Triki, S. Masmoudi, I. Ben Ayed
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S513
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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).
ObjectivesThe aim of this study is to consider TRAPPC9 deficiency in autosomal recessive ID with ASD.
MethodsWe 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.
ResultsA 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.
ConclusionsRepetitive 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 InterestNone Declared
Neuropsychiatric manifestations in Cornelia de Lange syndrome
- F. Majdoub, A. Souissi, M. Trabelsi, A. Ziadi, N. Belguith, F. Maazoul, M. Guirat, I. Boujelbene, H. Kamoun, R. Mrad, S. Masmoudi, I. Ben Ayed
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S512-S513
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- Article
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- You have access Access
- Open access
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Introduction
Cornelia De Lange syndrome (CdLS) is a dominant and rare genetically heterogeneous syndrome. It is characterized by a large phenotypical spectrum going from a classical to a non-classical form affecting multiple organ systems including central nervous, locomotor, skin, gastrointestinal, immune and endocrine systems in association with specific dysmorphic features. Neuropsychiatric manifestations represent a hallmark of CdLS phenotype.
ObjectivesThe aim of this study is to describe the neuropsychiatric features of Cornelia De Lange syndrome.
MethodsThis is a descriptive and retrospective study compromising unrelated Tunisian patients diagnosed clinically and genetically with CdLS during the period between 2002-2021. Each patient underwent a comprehensive clinical evaluation. In this study, we focused on neuropsychiatric and behavioural phenotype specifying intellectual disability(ID), language delay (LD), autism spectrum disorder (ASD), hyperactivity, aggressivity, specific learning disorder(SLD), sleep problems, compulsive behaviours and social anxiety disorders during adolescence.
ResultsA total of nine patients were included in this study. ID was present in all the evaluated patients with different level of severity evolving from mild (8/9) to severe (1/9). LD in absent of hearing problems was detected in two patients. Hyperactivity was found in three patients. Aggressivity was discovered in one patient in a form of self-injurious behaviour in one patient and hetero-aggressivity in another. None of our patients was diagnosed with ASD. Sleep problems such as frequent night-time awakenings were observed in one patient. All patients at age of schooling presented different levels of SLD. None of our patients was diagnosed with anxiety or compulsive behaviours.
ConclusionsOur results support the implication of behavioural and psychiatric features in CdLS phenotype. All of symptoms described in the literature were present in our patients. Further evaluation of our patients during their life is important to reveal age-related features such as anxiety or compulsive behaviours. These features can be used to inform specific psychiatric assistance for family psychoeducation, psycho-social interventions, and cognitive-behavioural education treatment approaches in individuals with CdLS.
Disclosure of InterestNone Declared