ArticleOrphanet journal of rare diseases2026
The ATP7B c.3316 G > A variant is associated with mild subphenotype in Wilson disease: a single-center cohort study.
Article in Orphanet journal of rare diseases, 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
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic studies have reported the ATP7B c.3316 G > A variant in Wilson disease (WD). However, the phenotypic characteristics of ATP7B c.3316 G > A remained unclear. We aimed to explore the ATP7B c.3316 G > A genotype-phenotype correlation and its clinical characteristics in patients of WD.
methodsA single-center cohort study enrolled 44 WD patients with c.3316 G > A variant from 43 unrelated Chinese families (19 males [43.2%], 25 females [56.8%]), and randomly selected 44 hospitalized WD patients with ATP7B mutations other than c.3316 G > A as the comparison group. All phenotypic data were collected before chelation therapy. Phenotypic analyses included age of onset, clinical subtype, Kayser-Fleischer ring (KFR), copper metabolism profiles (serum copper [SCu], serum copper oxidase [SCO], ceruloplasmin [CP]), Unified Wilson’s Disease Rating Scale Part I (UWDRS-I), and Child-Turcotte-Pugh (CTP) scores. Genotype-phenotype associations were quantified in subgroup analyses.
resultsThe c.3316 G > A cohort harbored 21 distinct ATP7B mutations, including 4 nonsense, 1 frameshift, 1 synonymous, and 15 missense variants. Group analysis showed that c.3316 G > A heterozygosity showed delayed age of onset compared with non-c.3316 G > A patients (p < 0.001), hepatic predominance over neurological presentations (p < 0.001), attenuated neurological severity (UWDRS-I: p = 0.001), lower KFR positivity (p = 0.033), and relatively elevated SCu, SCO, and CP (p < 0.001). No gender-related phenotypic disparities were observed within either cohort. Subgroup analysis within c.3316 G > A cohort, co-mutation with- (n = 20) versus without- (n = 24) c.2333 G > T revealed no significant differences in onset age, clinical subtypes, and copper metabolism profiles. Notably, cis-arranged relationship between c.3316 G > A and c.588C > A emerged via Haploview software (v4.2) (D’ = 1.0, LOD = 4.63, r2 = 0.239).
conclusionThe c.3316 G > A variant is associated with a distinct “mild” subphenotype characterized by delayed onset, neurologic sparing, lower KFR positivity, and milder copper dysregulation in patients of WD. Its cis-arranged relationship with the ATP7B c.588C > A variant provides critical insights into WD genetic diagnosis.
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.