ArticleMolecular genetics & genomic medicine2026
A Synonymous DLG4 Variant (c.771G>A) Causes Exon 9 Skipping via Paternal Germline Mosaicism in DLG4-Related Synaptopathy.
Article in Molecular genetics & genomic medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundThe synonymous DLG4 variant is annotated with conflicting pathogenicity interpretations, and its molecular mechanism remains uncharacterized. Paternal germline mosaicism has been inferred but never molecularly confirmed in DLG4-related synaptopathy.
objectiveTo functionally validate the pathogenicity of the synonymous DLG4 variant NM_001365.4:c.771G>A (p.Ala257=), and elucidate its inheritance mechanism in a proband with neurodevelopmental delay.
methodsWe performed trio-whole-exome sequencing in a proband with neurodevelopmental delay. The pathogenicity of the identified variant was assessed using bioinformatic predictors and validated through Sanger sequencing, RNA sequencing, and RT-PCR. The inheritance pattern was investigated via high-depth amplicon sequencing of paternal sperm DNA.
resultsThe synonymous DLG4 c.771G>A variant (absent in gnomAD) induced complete exon 9 skipping, resulting in a frameshift and premature termination codon. The variant was present at 3.83% variant allele frequency in paternal sperm, establishing paternal germline mosaicism as the origin.
conclusionOur study resolves conflicting interpretations of the DLG4 c.771G>A variant by demonstrating its pathogenic splice-disrupting effect. To our knowledge, this provides the first molecular confirmation of paternal germline mosaicism in DLG4-related synaptopathy. We note that maternal germline mosaicism was not assessed. These findings underscore the dual necessity of functional analysis for synonymous variants and sensitive mosaicism detection for accurate genetic counseling.
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.