ArticleHuman genomics2018
A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features.
Article in Human genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 71 citations in OpenAlex.
- DDX3X Syndrome: Clinical, Neuroimaging, AI-Assisted Facial Profiling and Genotype-Phenotype Correlations.Genes · 2026Observational
- Knockdown of Ddx3x in mPFC induces autistic-like phenotype in mice via altered synaptic plasticity.Translational psychiatry · 2026Article
- Article
- Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances inBiological psychiatry global open science · 2025Article
- DDX3X/MAVS alleviates doxorubicin‑induced cardiotoxicity by regulating stress granules.Molecular medicine reports · 2025Article
- Expanding the understanding of DDX3X-related neurodevelopmental disorder in males.European journal of human genetics : EJHG · 2025Article
- DDX3X-related neurodevelopmental disorder in males - presenting a new cohort of 19 males and a literature review.European journal of human genetics : EJHG · 2025Article
- Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X.Nature communications · 2025Article
- Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicasesGenome research · 2025Article
- Multi-modal investigation reveals pathogenic features of diverse DDX3X missense mutations.PLoS genetics · 2025Article
- First Diagnostic Questionnaire for Assessing Patients' Social Functioning: Comprehensive DDX3X Syndrome Patient Profile.Journal of clinical medicine · 2024Article
- DDX3X syndrome: From clinical phenotypes to biological insights.Journal of neurochemistry · 2024Review
- Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicasesbioRxiv : the preprint server for biology · 2024Article
- Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Lessons from two series by physicians and caregivers' self-reported data in DDX3X-related disorders.Molecular genetics & genomic medicine · 2024Article
- Dandy-Walker Malformation in a Girl withMolecular syndromology · 2023Article
- DDX3X Syndrome Behavioral Manifestations with Particular Emphasis on Psycho-Pathological Symptoms-A Review.Biomedicines · 2023Review
- The impact of chromosomal sex on cardiometabolic health and disease.Trends in endocrinology and metabolism: TEM · 2023Review
- Social and emotional characteristics of girls and young women with DDX3X-associated intellectual disability: a descriptive and comparative study.Journal of autism and developmental disorders · 2023Article
- Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundIntellectual disability (ID) is a common condition with a population prevalence frequency of 1-3% and an enrichment for males, driven in part by the contribution of mutant alleles on the X-chromosome. Among the more than 500 genes associated with ID, DDX3X represents an outlier in sex specificity. Nearly all reported pathogenic variants of DDX3X are de novo, affect mostly females, and appear to be loss of function variants, consistent with the hypothesis that haploinsufficiency at this locus on the X-chromosome is likely to be lethal in males.
resultsWe evaluated two male siblings with syndromic features characterized by mild-to-moderate ID and progressive spasticity. Quad-based whole-exome sequencing revealed a maternally inherited missense variant encoding p.R79K in DDX3X in both siblings and no other apparent pathogenic variants. We assessed its possible relevance to their phenotype using an established functional assay for DDX3X activity in zebrafish embryos and found that this allele causes a partial loss of DDX3X function and thus represents a hypomorphic variant.
conclusionsOur genetic and functional data suggest that partial loss of function of DDX3X can cause syndromic ID. The p.R79K allele affects a region of the protein outside the critical RNA helicase domain, offering a credible explanation for the observed retention of partial function, viability in hemizygous males, and lack of pathology in females. These findings expand the gender spectrum of pathology of this locus and suggest that analysis for DDX3X variants should be considered relevant for both males and females.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.