Evidence map›Paper›PMID 42684564›Full record

ArticleNeurogenetics2026

Potential contributors to variable penetrance of NOTCH3 p.Arg1231Cys Variant.

Jeongyeon Hwang, Ayuko Iverson, Amy Woroch, Ophir Keret, Fanny M Elahi, Georges Naasan

Abstract readCase Reports
PubMed Publisher
In one paragraph

Article in Neurogenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Jeongyeon HwangThe Barbara and Maurice Deane Center for Wellness and Cognitive Health, Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98 Street, 7th Floor, New York, NY, 10029, USA. jhwang22@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-0551-3660
Ayuko IversonDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
Amy WorochDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
Ophir KeretThe Barbara and Maurice Deane Center for Wellness and Cognitive Health, Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98 Street, 7th Floor, New York, NY, 10029, USA.
Fanny M ElahiThe Barbara and Maurice Deane Center for Wellness and Cognitive Health, Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98 Street, 7th Floor, New York, NY, 10029, USA.
Georges NaasanThe Barbara and Maurice Deane Center for Wellness and Cognitive Health, Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98 Street, 7th Floor, New York, NY, 10029, USA.

Funding

Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Margaret Sewell · 2020 to 2026
$31.0M
NIA NIH HHS P30 AG066514
6 · The paper itself

Abstract

Missense mutations in NOTCH3, especially cysteine-altering pathogenic variants, are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The NOTCH3 p.Arg1231Cys variant, located in EGFr domain 31, is classified as low-risk under the three-tiered EGFr domain risk stratification system. We report two cases of p.Arg1231Cys heterozygosity presenting with early-onset dementia, strokes, and extensive leukoencephalopathy. These cases highlight the potential contributing factors to increasing penetrance of p.Arg1231Cys variant, and the need for functional evaluation to improve the clinical utility of genetic testing in hereditary small vessel disease.

Indexed as

CADASILMutation, MissensePenetranceReceptor, Notch3HumansNOTCH3 protein, humanReceptor, Notch3Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)Cys-altering NOTCH3 variantsp.Arg1231Cys variantVariable penetrance

Identifiers

PMID42684564

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.