Evidence map›Paper›PMID 41499643›Full record

ArticleClinical genetics2026

Biallelic COL4A2 Variants Associated With Brain Small Vessel Disease and Brain Malformations.

Anees Muhammad, Mohammad Sadegh Shams Nosrati, Alireza Dostmohammadi, Reihaneh Khorasanian, Mariasavina Severino, Morteza Doustmohammadi, Francesca Madia, Siddharth Srivastava, Aisling Quinlan, Dario Paladini and 2 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

12 authors.

Anees MuhammadInstitute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
Mohammad Sadegh Shams NosratiDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Alireza DostmohammadiDepartment of Bioinformatics and Computational Biophysics, Faculty of Biology and Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
Reihaneh KhorasanianDepartment of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mariasavina SeverinoNeuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Morteza DoustmohammadiSchool of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
Francesca MadiaMedical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Siddharth SrivastavaDepartment of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
Aisling QuinlanDepartment of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
Dario PaladiniFetal Medicine and Surgery Unit, Department Mother and Child, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Federico ZaraDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Marcello ScalaDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.ORCID 0000-0003-2194-7239

Funding

Investigating the Genetic Landscape of Cerebral PalsyK23NS119666 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI SRIVASTAVA, SIDDHARTH · 2021 to 2025
$1.1M
NINDS NIH HHS K23 NS119666
6 · The paper itself

Abstract

Deleterious variants in COL4A2, encoding type IV collagen's alpha-2 chain, cause heterogeneous cerebrovascular and developmental brain malformations. While many dominant variants are known, biallelic changes are rarely reported. We reported two severe cases: Case #1, an aborted fetus with cerebral calcifications, hemorrhages, periventricular leukomalacia, and cerebellar disruption; and Patient #2, a 2-year-old girl with neurodevelopmental impairment, cortical malformations (frontal schizencephaly, polymicrogyria), and reduced white matter volume. Exome sequencing identified a homozygous missense COL4A2 variant in case #1 and compound heterozygous loss-of-function variants (splicing and truncating) in case #2. All variants were rare and predicted to affect protein stability and function in silico. Our cases reinforce the association between biallelic COL4A2 variants and brain small vessel disease, expanding the recessive COL4A2-related phenotype to include cortical malformations.

Indexed as

BrainCerebral Small Vessel DiseasesCollagen Type IVGenetic Predisposition to DiseaseAllelesChild, PreschoolExome SequencingFemaleHumansPhenotypeCOL4A2 protein, humanCollagen Type IVbrain hemorrhagebrain small vessel diseaseCOL4A2collagen type IVcortical malformationsrecessive variants

Identifiers

PMID41499643
PMCPMC12779229

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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.