Evidence map›Paper›PMID 40879451›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2025

Loss of ANK3 Function Causes a Recessive Neurodevelopmental Disorder with Cerebellar Ataxia.

Reza Maroofian, Giulia Spoto, Dalila Moualek, Maha S Zaki, Asthik Biswas, Felice D'Arco, Sajjad Biglari, Pooneh Nikuei, Joseph G Gleeson, Meriem Tazir and 2 more

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In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2025. 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.

Reza MaroofianDepartment of Neuromuscular Diseases, University College London, Queen Square, Institute of Neurology, London, UK.
Giulia SpotoDepartment of Neuromuscular Diseases, University College London, Queen Square, Institute of Neurology, London, UK.ORCID https://orcid.org/0009-0003-6714-6952
Dalila MoualekService de Neurologie, CHU Mustapha Bacha, Alger, Algeria.
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Asthik BiswasPediatric Neuroradiology Unit, Radiology Department, Great Ormond Street Hospital for Children, London, UK.
Felice D'ArcoPediatric Neuroradiology Unit, Radiology Department, Great Ormond Street Hospital for Children, London, UK.
Sajjad BiglariDepartment of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.
Pooneh NikueiMolecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Joseph G GleesonRady Children's Institute for Genomic Medicine, San Diego, California, USA.
Meriem TazirService de Neurologie, CHU Mustapha Bacha, Alger, Algeria.
Lamia Ali PachaService de Neurologie, CHU Mustapha Bacha, Alger, Algeria.
Henry HouldenDepartment of Neuromuscular Diseases, University College London, Queen Square, Institute of Neurology, London, UK.ORCID https://orcid.org/0000-0002-2866-7777

Funding

Molecular Characterization of Pontocerebellar HypoplasiaR01NS098004 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOSEPH G GLEESON · 2016 to 2026
$4.6M
NINDS NIH HHS R01 NS098004Wellcome Trust
6 · The paper itself

Abstract

backgroundANK3 encodes ankyrin-G, a key scaffolding protein essential for neuronal function. While both monoallelic and biallelic ANK3 variants have been linked to neurodevelopmental disorders (NDDs), existing evidence for their pathogenicity and clinical correlation remains limited and heterogeneous.

objectiveTo delineate the clinical features associated with biallelic ANK3 predicted loss-of-function (pLOF) variants.

methodsWe employed exome sequencing, Sanger validation, detailed clinical phenotyping, and extensive international data sharing to identify patients with biallelic ANK3 variants.

resultsWe describe five individuals from three unrelated consanguineous families with segregating homozygous ANK3 pLOF variants. These patients presented with a relatively consistent phenotype comprising developmental delay, intellectual disability, hypotonia, variable epilepsy, and cerebellar signs including ataxia, tremor, and dysarthria. Among the three patients for whom brain magnetic resonance imaging was available, cerebellar atrophy was observed, predominantly affecting the superior vermis and cerebellar hemispheres. These clinical findings align with murine models lacking the cerebellar ankyrin-G isoform, which similarly exhibit ataxic features and high cerebellar ANK3 expression.

conclusionOur findings support a recognizable NDD with non-progressive cerebellar ataxia linked to biallelic ANK3 pLOF variants. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

AnkyrinsCerebellar AtaxiaLoss of Function MutationNeurodevelopmental DisordersAdolescentCerebellumChildChild, PreschoolDevelopmental DisabilitiesFemaleHumansMalePedigreePhenotypeANK3 protein, humanAnkyrinsANK3cerebellar ataxiacerebellar atrophyneurodevelopmental disorder

Identifiers

PMID40879451
PMCPMC12661628

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Registered trials

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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.