ArticleJournal of the Chinese Medical Association : JCMA2026
An in trans NOTCH3 loss-of-function variant modifies disease severity in CADASIL: A family-based study.
Article in Journal of the Chinese Medical Association : JCMA, 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
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by pathogenic NOTCH3 variants, most commonly heterozygous cysteine-altering variants. Disease severity varies widely, and the impact of reduced NOTCH3 dosage on CADASIL severity remains unclear. We describe a family of four individuals carrying a cysteine-altering NOTCH3 variant and/or a frameshift loss-of-function (LoF) variant, demonstrating marked intrafamilial phenotypic heterogeneity.
methodsFour related individuals underwent standardized clinical assessment, brain magnetic resonance imaging (MRI), genetic analysis, skin biopsy, and NOTCH3 complementary DNA (cDNA) sequencing.
resultsThe proband, carrying p.Cys1146Ser and p.Cys1024Valfs248 in trans, developed progressive gait disturbance, dysphagia, and slurred speech beginning in his mid-thirties. Brain MRI demonstrated extensive white matter hyperintensities, multiple lacunar infarcts, and numerous cerebral microbleeds. In contrast, the father (carrying p.Cys1146Ser alone) and the mother and brother (carrying p.Cys1024Valfs248 alone) exhibited milder clinical and imaging phenotypes. Only the carriers of the cysteine-altering variant demonstrated NOTCH3 extracellular domain (NOTCH3 ECD ) immunoreactivity in skin vessels. NOTCH3 cDNA sequencing from the skin tissue demonstrated reduced LoF allele expression.
conclusionReduced NOTCH3 dosage may modify the disease severity of CADASIL.
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.