ArticleAmerican journal of human genetics2015
Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Large-scale genome-wide analyses of stuttering.Nature genetics · 2025Pooled it
- Developmental stuttering with common and complex phenotypes.Developmental medicine and child neurology · 2026Article
- De novo protein-coding gene variants in developmental stuttering.Molecular psychiatry · 2026Article
- Article
- Challenges and Opportunities in Characterizing the Genetics of Stuttering: From Sample Acquisition to Functional Interpretation of the Genome.Journal of speech, language, and hearing research : JSLHR · 2025Review
- Unraveling Stuttering Through a Multi-Omics Lens.Life (Basel, Switzerland) · 2025Article
- Identification of comorbid genes between type 2 diabetes and migraine through peripheral blood single-cell and Mendelian randomization analysis.The journal of headache and pain · 2025Article
- Stuttering: Our Current Knowledge, Research Opportunities, and Ways to Address Critical Gaps.Neurobiology of language (Cambridge, Mass.) · 2025Review
- Atypical gut microbiota composition in a mouse model of developmental stuttering.Scientific reports · 2024Article
- Whole Genome Analysis in Consanguineous Families Reveals New Loci for Speech Sound Disorder (SSD).Genes · 2024Article
- Knowns and unknowns about the neurobiology of stuttering.PLoS biology · 2024Article
- Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40.Brain : a journal of neurology · 2023Article
- Precision Medicine as a New Frontier in Speech-Language Pathology: How Applying Insights From Behavior Genomics Can Improve Outcomes in Communication Disorders.American journal of speech-language pathology · 2023Article
- Stuttering as a spectrum disorder: A hypothesis.Current research in neurobiology · 2023Review
- Article
- The adaptor protein chaperone AAGAB stabilizes AP-4 complex subunits.Molecular biology of the cell · 2022Article
- Atypical development of Broca's area in a large family with inherited stuttering.Brain : a journal of neurology · 2022Article
- Population-based genetic effects for developmental stuttering.HGG advances · 2022Article
- Family-Based Whole-Exome Analysis of Specific Language Impairment (SLI) Identifies Rare Variants inBrain sciences · 2021Article
- Phenome risk classification enables phenotypic imputation and gene discovery in developmental stuttering.American journal of human genetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of-function mutations in this gene. AP4E1 encodes the ε subunit of the heterotetrameric (ε-β4-μ4-σ4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the μ4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6-phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering.
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.