A de novo DDX3X Variant Is Associated With Syndromic Intellectual Disability: Case Report and Literature Review

Chen, Yun; Liu, Kaiyu; Yang, Zailan; Li, Xiaohuan; Xu, Rui; Zhou, Hao

doi:10.3389/fped.2020.00303

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…Genetic conditions linked to sleep disturbances include people with Down's Syndrome with and without obstructive sleep apnoea (Al‐Khudhairy et al, 2019; Bassell et al, 2015; Chawla, Howard, et al, 2021; Esbensen et al, 2018; Heubi et al, 2021; Stores, 2019; Worley et al, 2015), Tuberous sclerosis complex (Trickett et al, 2018), Mowat–Wilson Syndrome (Di Pisa et al, 2019; Evans et al, 2016), Cornelia de Lange Syndrome (Zambrelli et al, 2016), Angelman syndrome (den Bakker et al, 2018; den Bestern et al, 2021; Levin et al, 2022; Pearson et al, 2018; Trickett et al, 2018), Smith‐Magenis syndrome (Mullegama et al, 2015; Rive Le Gouard et al, 2021; Smith et al, 2019; Trickett et al, 2020), Fragile X syndrome (Budimirovic et al, 2022; Mullegama et al, 2015). In addition to rare conditions which are linked to sleep disturbances such as Christianson Syndrome (Gruber et al, 2022), Dup15q Syndrome (Barstein et al, 2021), Pallister‐Killian Syndrome (Fetta et al, 2022), Phelan‐McDermid Syndrome and SYNGAP1‐ID (Smith‐Hicks et al, 2021), MBD5‐associated neurodevelopmental disorder (Gandhi et al, 2021), Arboleda‐Tham syndrome (Smith & Harris, 2021), Bosch‐Boonstra‐Schaaf optic atrophy syndrome (Rech et al, 2020) and emerging genetic variants including microdeletion syndrome at 2q22.1q22.3 and de novo DDX3X variants (Chen et al, 2020; Verhoeven et al, 2020). This shows that a wide array of specific intellectual disability syndromes are associated with sleep problems, although variation from night to night and within syndrome groupings is found (Trickett et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

Behavioural sleep problems in children and adults with intellectual disabilities: An integrative literature review

Harper

McAnelly

Walshe

et al. 2023

Research Intellect Disabil

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Background People with intellectual disabilities are more likely to experience sleep problems, which can affect quality of life, physical health, mental health and well‐being. Methods An integrative literature review was conducted to investigate what is known about behavioural sleep disturbances in people with an intellectual disability. The search used the following databases: Scopus, PsycInfo and Cinahl, to find papers published since 2015. Results Within intellectual disability research, sleep appears as a common issue due to its high prevalence, negative relationships with an individual's physical and mental health, their quality of life, and impact of sleep problems on family or carers. The growing evidence base appears to support the use of behavioural, lifestyle and pharmacological interventions to improve sleep in people with an intellectual disability. Conclusion A wide array of literature provides evidence that people with intellectual disabilities are affected by and need support with their sleep.

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Section: Resultsmentioning

confidence: 99%

Behavioural sleep problems in children and adults with intellectual disabilities: An integrative literature review

Harper

McAnelly

Walshe

et al. 2023

Research Intellect Disabil

View full text Add to dashboard Cite

show abstract

“…This could be interpreted by different pathogenic mechanisms. Many aberrant truncating mRNAs (i.e., frameshift or non-sense variants) might undergo non-sense-mediated RNA decay (NMD) and resulted in a haploinsufficiency effect, while a subset of missense variants could function in a dominant-negative manner ( Chen et al, 2020 ; Lennox et al, 2020 ). Further investigations about gain-of-function mechanism behind certain missense mutations will be carried out by modeling missense mutations in mice.…”

Section: Discussionmentioning

confidence: 99%

Expansion of Clinical and Genetic Spectrum of DDX3X Neurodevelopmental Disorder in 23 Chinese Patients

Dai

Yang

Guo

et al. 2022

Front. Mol. Neurosci.

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AimDe novo DDX3X variants account for 1–3% of unexplained intellectual disability cases in females and very rarely in males. Yet, the clinical and genetic features of DDX3X neurodevelopmental disorder in the Chinese cohort have not been characterized.MethodA total of 23 Chinese patients (i.e., 22 female and 1 male) with 22 de novo DDX3X deleterious variants were detected among 2,317 probands with unexplained intellectual disability (ID) undertaking whole exome sequencing (WES). The age, sex, genetic data, feeding situation, growth, developmental conditions, and auxiliary examinations of the cohort were collected. The Chinese version of the Gesell Development Diagnosis Scale (GDDS-C) was used to evaluate neurodevelopment of DDX3X patients. The Social Communication Questionnaire (SCQ)-Lifetime version was applied as a primary screener to assess risk for autism spectrum disorder (ASD).ResultA total of 17 DDX3X variants were novel and 22 were de novo. Missense variants overall were only slightly more common than loss-of-function variants and were mainly located in two functional subdomains. The average age of this cohort was 2.67 (±1.42) years old. The overlapping phenotypic spectrum between this cohort and previously described reports includes intellectual disability (23/23, 100%) with varying degrees of severity, muscle tone abnormalities (17/23, 73.9%), feeding difficulties (13/23, 56.5%), ophthalmologic problems (11/23, 47.8%), and seizures (6/23, 26.1%). A total of 15 individuals had notable brain anatomical disruption (15/23, 65.2%), including lateral ventricle enlargement, corpus callosum abnormalities, and delayed myelination. Furthermore, 9 patients showed abnormal electroencephalogram results (9/23, 39.1%). Hypothyroidism was first noted as a novel clinical feature (6/23, 26.1%). The five primary neurodevelopmental domains of GDDS-C in 21 patients were impaired severely, and 13 individuals were above the “at-risk” threshold for ASD.InterpretationAlthough a certain degree of phenotypic overlap with previously reported cohorts, our study described the phenotypic and variation spectrum of 23 additional individuals carrying DDX3X variants in the Chinese population, adding hypothyroidism as a novel finding. We confirmed the importance of DDX3X as a pathogenic gene in unexplained intellectual disability, supporting the necessity of the application of WES in patients with unexplained intellectual disability.

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Control of the eIF4E activity: structural insights and pharmacological implications

Romagnoli

D’Agostino

Ardiccioni

et al. 2021

Cell. Mol. Life Sci.

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The central role of eukaryotic translation initiation factor 4E (eIF4E) in controlling mRNA translation has been clearly assessed in the last decades. eIF4E function is essential for numerous physiological processes, such as protein synthesis, cellular growth and differentiation; dysregulation of its activity has been linked to ageing, cancer onset and progression and neurodevelopmental disorders, such as autism spectrum disorder (ASD) and Fragile X Syndrome (FXS). The interaction between eIF4E and the eukaryotic initiation factor 4G (eIF4G) is crucial for the assembly of the translational machinery, the initial step of mRNA translation. A well-characterized group of proteins, named 4E-binding proteins (4E-BPs), inhibits the eIF4E–eIF4G interaction by competing for the same binding site on the eIF4E surface. 4E-BPs and eIF4G share a single canonical motif for the interaction with a conserved hydrophobic patch of eIF4E. However, a second non-canonical and not conserved binding motif was recently detected for eIF4G and several 4E-BPs. Here, we review the structural features of the interaction between eIF4E and its molecular partners eIF4G and 4E-BPs, focusing on the implications of the recent structural and biochemical evidence for the development of new therapeutic strategies. The design of novel eIF4E-targeting molecules that inhibit translation might provide new avenues for the treatment of several conditions.

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A de novo DDX3X Variant Is Associated With Syndromic Intellectual Disability: Case Report and Literature Review

Cited by 7 publications

References 31 publications

Behavioural sleep problems in children and adults with intellectual disabilities: An integrative literature review

Behavioural sleep problems in children and adults with intellectual disabilities: An integrative literature review

Expansion of Clinical and Genetic Spectrum of DDX3X Neurodevelopmental Disorder in 23 Chinese Patients

Control of the eIF4E activity: structural insights and pharmacological implications

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