Evidence mapPaperPMID 41715124Full record

ArticleJournal of translational medicine2026

Novel genetic variants identification and immune profiling in ataxia telangiectasia patients.

Rim Jenni, Hedia Klaa, Asma Chikhaoui, Khouloud Zayoud, Emmanuelle Cochet, Ichraf Kraoua, Lydie Burglen, Houda Yacoub-Youssef

Abstract read
In one paragraph

Article in Journal of translational medicine, 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

8 authors.

Rim JenniLaboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, University Tunis El Manar, Tunis, 1002, Tunisia.
Hedia KlaaLR18SP04 and Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, 1007, Tunisia.
Asma ChikhaouiLaboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, University Tunis El Manar, Tunis, 1002, Tunisia.
Khouloud ZayoudLaboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, University Tunis El Manar, Tunis, 1002, Tunisia.
Emmanuelle CochetUnit of Pediatric Neurogenetics, Department of Genetics, Trousseau Hospital, APHP.Sorbonne University, Paris, 75012, France.
Ichraf KraouaLR18SP04 and Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis, 1007, Tunisia.
Lydie BurglenReference Center for Malformations and Congenital Diseases of the Cerebellum and Unit of Pediatric Neurogenetics, Department of Genetics, Trousseau Hospital, APHP. Sorbonne University, Paris, 75012, France.
Houda Yacoub-YoussefLaboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, University Tunis El Manar, Tunis, 1002, Tunisia. houda.yacoub@pasteur.utm.tn.ORCID http://orcid.org/0000-0001-5351-4775

Funding

Ministère de l'Enseignement Supérieur et de la Recherche Scientifique-TUBITAK GENEX-ARCA 2024_2027
6 · The paper itself

Abstract

backgroundAtaxia telangiectasia (AT) is an autosomal recessive neurodegenerative disease. While heterozygous relatives of AT patients are known to be clinically healthy, a predisposition to various pathologies has been reported. Our aim was firstly, to further characterize the clinical features and broaden the spectrum of genetic pathogenic variants in AT patients. Secondly, we aimed to study the immune profiles of AT patients and their relatives to identify similarities or common biomarkers.

methodsA Target Gene Sequencing for six patients suspected with AT was performed. Computational analysis was conducted to assess the pathogenicity of novel variants. The distribution of immune cells was assessed by flow cytometry in patients with AT, AT-like disorder, Friedreich ataxia, and in AT relatives. The expression pattern of candidate genes was evaluated by RT-qPCR.

resultsWe identified and predicted the pathogenicity of novel variants in the ATM gene. Computational analysis suggested that the novel identified missense mutation could affect ATP binding pattern and ATM protein flexibility, while Alu element insertion could probably induces a premature stop codon. Furthermore, our results confirm the pathogenic effect of identified splicing mutations on the ATM transcript. Moreover, we noticed a high percentage of LTCD4 + and LTCD8 + senescent subsets in AT patients and a relative increase of the of intermediate and non-classical monocytes accompanied with a decrease of classical monocytes specifically in AT patients with truncated biallelic mutations which was intriguingly similar to the immune profile of AT parents. In addition, a difference of immune pattern was observed between AT patients with biallelic truncated mutations compared to those with at least one non-truncated mutation, with a variability intragroup. Gene expression analysis identified FOXO3, IL33 and METTL3 as putative genes that may yield clues into AT pathogenesis.

conclusionTaken together, our study expands the mutational spectrum of AT disease worldwide and further characterize the immune profile of AT patients uncovering a possible difference in some immune cellular subsets related to ATM mutation type and delineate putative immune abnormalities related to ATM heterozygosity among AT parents. Furthermore, dysregulation in FOXO3, IL33 and METTL3 expression could be related to disease severity.

Indexed as

Ataxia TelangiectasiaGenetic VariationAdolescentAdultAtaxia Telangiectasia Mutated ProteinsBase SequenceChildFemaleHumansMaleMutationAtaxia Telangiectasia Mutated ProteinsAtaxia telangiectasiaATMBioinformaticsGene expression analysisImmunophenotyping

Identifiers

PMID41715124
PMCPMC13020073

What Socratic holds

Textmetadata
LicenceCC BY
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.