Genotype-phenotype correlations and protein domain-level predictors of cerebrovascular malformations in hereditary hemorrhagic telangiectasia.
Overview
- Department of Neurosurgery, Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, L.go A. Gemelli 8, 00168 Rome, Italy
- Department of Neurosciences, Imaging and Clinical Sciences, G. D’Annunzio University, Chieti-Pescara, Italy
- UOC Genetica MedicaDipartimento di Scienze della Vita e Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Unit of Internal Medicine, Cristo Re Hospital, 00167 Rome, Italy
- Department of Aging, Orthopedic, and Rheumatologic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Abstract
Background: Hereditary Hemorrhagic Telangiectasia (HHT) exhibits marked phenotypic heterogeneity. Although gene–organ associations are well established for visceral involvement, predictors of cerebrovascular malformations (CVMs), particularly brain arteriovenous malformations (bAVMs), remain incompletely defined. This study aimed to investigate genotype–phenotype correlations and identify predictors of bAVMs in a genetically confirmed HHT cohort.
Methods: We conducted a retrospective analysis of 142 Caucasian patients with genetically confirmed HHT. Clinical manifestations were systematically assessed and correlated with the mutated gene (ENG, ACVRL1, and SMAD4), variant type (truncating vs. non-truncating), and protein domain location. Multivariable logistic regression was performed to identify independent predictors of bAVMs.
Results: The cohort included 83 (58.5%) ACVRL1 and 53 (37.3%) ENG mutation carriers. Bivariate analysis demonstrated distinct phenotypic patterns. ENG mutations were strongly associated with pulmonary AVMs (p < 0.001) and bAVMs (p < 0.001), with bAVMs observed in 35.8% of ENG carriers compared with 3.6% of ACVRL1 carriers. In contrast, hepatic AVMs were more frequent among ACVRL1 carriers (44.6%), although this did not reach statistical significance (p = 0.086). In the multivariable logistic regression model (overall p < 0.001), younger age emerged as the sole independent predictor of bAVMs (OR 0.968, p = 0.040), whereas the mutated gene did not retain independent significance.
Conclusion: ENG mutation carriers display a markedly increased cerebrovascular burden, confirming a gene-specific susceptibility to bAVMs. Younger age independently predicts bAVM presence. These findings support age- and genotype-informed risk stratification and may help refine screening strategies in HHT patients.
Supplementary Information: The online version contains supplementary material available at 10.1007/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
No file of the authors' code could be read here: it is described below, and read at its source.
Zenodo 22100478
Availability: 1 check, the latest on 30 September 2026: the link answers (HTTP 200)
- 30 September 2026: the link answers (HTTP 200)
Zenodo 22100477
Availability: 1 check, the latest on 30 September 2026: the link answers (HTTP 200)
- 30 September 2026: the link answers (HTTP 200)
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 2 repositories of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 0 scripts, each with its path and the digest of its content;
- no match between paragraphs and code yet;
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
No dataset and no data link were found in the paper.
Availability of data and materials
The datasets used and/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 4 keywords, 16 MeSH terms, 1 funder, 21 references.
Cite
This paper
Sturiale, C. L., Cocilovo, F., Trevisi, G., Palermo, M., Cordisco, E. L., Di Martino, L., Sonnini, E., Albanese, A., Doglietto, F., Pola, R., & Gaetani, E. (2026). Genotype-phenotype correlations and protein domain-level predictors of cerebrovascular malformations in hereditary hemorrhagic telangiectasia. Journal of neurology, 273(4), 237. https://
BibTeX
@article{sturiale2026gen
author = {Sturiale, Carmelo Lucio and Cocilovo, Federico and Trevisi, Gianluca and Palermo, Matteo and Cordisco, Emanuela Lucci and Di Martino, Luigi and Sonnini, Elena and Albanese, Alessio and Doglietto, Francesco and Pola, Roberto and Gaetani, Eleonora},
title = {{Genotype-phenotype correlations and protein domain-level predictors of cerebrovascular malformations in hereditary hemorrhagic telangiectasia}},
journal = {Journal of neurology},
year = {2026},
month = mar,
volume = {273},
number = {4},
pages = {237},
publisher = {Springer Science+Business Media},
issn = {0340-5354},
doi = {10.1007/
url = {https://
pmid = {41915210},
pmcid = {PMC13038781}
}
RIS
TY - JOUR
AU - Sturiale, Carmelo Lucio
AU - Cocilovo, Federico
AU - Trevisi, Gianluca
AU - Palermo, Matteo
AU - Cordisco, Emanuela Lucci
AU - Di Martino, Luigi
AU - Sonnini, Elena
AU - Albanese, Alessio
AU - Doglietto, Francesco
AU - Pola, Roberto
AU - Gaetani, Eleonora
TI - Genotype-phenotype correlations and protein domain-level predictors of cerebrovascular malformations in hereditary hemorrhagic telangiectasia
T2 - Journal of neurology
J2 - J Neurol
PY - 2026
DA - 2026/
VL - 273
IS - 4
SP - 237
SN - 0340-5354
PB - Springer Science+Business Media
DO - 10.1007/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1007/
"type": "article-journal",
"title": "Genotype-phenotype correlations and protein domain-level predictors of cerebrovascular malformations in hereditary hemorrhagic telangiectasia",
"container-title": "Journal of neurology",
"author": [
{
"family": "Sturiale",
"given": "Carmelo Lucio"
},
{
"family": "Cocilovo",
"given": "Federico"
},
{
"family": "Trevisi",
"given": "Gianluca"
},
{
"family": "Palermo",
"given": "Matteo"
},
{
"family": "Cordisco",
"given": "Emanuela Lucci"
},
{
"family": "Di Martino",
"given": "Luigi"
},
{
"family": "Sonnini",
"given": "Elena"
},
{
"family": "Albanese",
"given": "Alessio"
},
{
"family": "Doglietto",
"given": "Francesco"
},
{
"family": "Pola",
"given": "Roberto"
},
{
"family": "Gaetani",
"given": "Eleonora"
}
],
"container-title-short":
"volume": "273",
"issue": "4",
"page": "237",
"DOI": "10.1007/
"PMID": "41915210",
"PMCID": "PMC13038781",
"ISSN": "0340-5354",
"publisher": "Springer Science+Business Media",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
3,
31
]
]
}
}
The tracing map gets a citation of its own once an author has validated it and it has a DOI.
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1186/s40478-023-01531-y
- Exceptionally rare IDH1-mutant adult medulloblastoma with concurrent GNAS mutation revealed by in vivo magnetic resonance spectroscopy and deep sequencing.Journal: Acta neuropathologica communicationsIn common: genetics / omics, author Francesco Doglietto
- [2] doi:10.3389/fneur.2022.867048
- Neuroplasticity Mechanisms in Frontal Brain Gliomas: A Preliminary Study.Journal: Frontiers in neurologyIn common: author Carmelo Lucio Sturiale
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Validate its tracing map
You validate the map as this page shows it: 2 repositories of the authors' code, each at its verified commit and with its license, 0 scripts, and 0 matches between paragraphs and code (see the Code and Map sections). It then receives a DOI on Zenodo, with you (your ORCID iD) and OSCR as its creators; the code itself is not deposited.
The map's fingerprint: sha256:e0876bfb221968ed…
Add the badge to the code's README
If you are an author or a maintainer of this paper's code, you can add this badge. It says what OSCR knows of the paper (its code, its validated tracing map) and links the code to this page. Paste one of these snippets under the README's title. Keep the two marks around it, so that the badge can be replaced in place and is never added twice. OSCR changes nothing in your repository.
Markdown
<!-- oscr-badge:start -->
[](https://openscicode.org/badge/doi/10.1007/s00415-026-13777-2)
<!-- oscr-badge:end -->reStructuredText
.. oscr-badge:start
.. image:: https://openscicode.org/badge/doi/10.1007/s00415-026-13777-2.svg
:target: https://openscicode.org/badge/doi/10.1007/s00415-026-13777-2
:alt: OSCR
.. oscr-badge:endHTML
<!-- oscr-badge:start -->
<a href="https://openscicode.org/badge/doi/10.1007/s00415-026-13777-2"><img src="https://openscicode.org/badge/doi/10.1007/s00415-026-13777-2.svg" alt="OSCR"></a>
<!-- oscr-badge:end -->If you choose to, you can have the badge kept up to date for you, with oscr badge --write from the command line or with the GitHub Action in your repository's workflows. Every other form and option (a card, AsciiDoc, LaTeX, shields.io) is on the badge page.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: code errors and mismatches between the code and the paper about this paper and its code, from readers and its authors, beside the paper and its tracing map.
Report a mismatch between the code and the paper · Report a code error (signed in)
Reproductions: reports from readers who ran the authors' code and did not get the paper's result, what they ran, with which environment, commit and data.
Report a reproduction failure (signed in)
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.