Evidence map›Paper›PMID 39985054›Full record

ArticleMolecular cytogenetics2025

Prevalence of CNVs on the X chromosome in patients with neurodevelopmental disorders.

Ekaterina N Tolmacheva, Anna A Kashevarova, Elizaveta A Fonova, Olga A Salyukova, Gulnara N Seitova, Lyudmila P Nazarenko, Anna A Agafonova, Larisa I Minaycheva, Ekaterina G Ravzhaeva, Valeria V Petrova and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cytogenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

2 citing papers in PubMed.

  1. Article
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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

17 authors.

Ekaterina N TolmachevaLaboratory of Cytogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Ushaika Street 10, Tomsk, 634050, Russia. kate.tolmacheva@medgenetics.ru.
Anna A KashevarovaLaboratory of Cytogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Ushaika Street 10, Tomsk, 634050, Russia.
Elizaveta A FonovaLaboratory of Genomics of Orphan Diseases, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Olga A SalyukovaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Gulnara N SeitovaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Lyudmila P NazarenkoMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Anna A AgafonovaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Larisa I MinaychevaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Ekaterina G RavzhaevaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Valeria V PetrovaMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Maria E LopatkinaLaboratory of Ontogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Elena O BelyaevaLaboratory of Ontogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Svetlana L VovkMedical Genetic Center (Genetic Clinic), Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Dmitry A FedotovLaboratory of Ontogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Oksana Y VasilyevaLaboratory of Cytogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Ushaika Street 10, Tomsk, 634050, Russia.
Nikolay A SkryabinLaboratory of Genomics of Orphan Diseases, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.
Igor N LebedevLaboratory of Ontogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634050, Russia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe X chromosome is enriched with genes related to brain development, and the hemizygous state of these genes in men causes some difficulties in the clinical interpretation of copy number variations (CNVs). In this study, we present data on the frequency and spectrum of CNVs on the X chromosome in a cohort of patients with neurodevelopmental disorders (NDDs).

methodsChromosomal microarray analysis was performed for 1175 patients with NDDs. CNVs were confirmed by real-time quantitative PCR. X chromosome inactivation was analysed by methyl-sensitive PCR. To determine the pathogenic significance of the CNVs, several criteria, including the origin (inherited or de novo), variant type (microdeletion or microduplication), and X chromosome inactivation pattern in asymptomatic and symptomatic carriers, were considered. Additionally, the spectrum, size and molecular bases of copy number changes in genes or gene regions involved in the development of the pathological phenotype in each patient were considered.

resultsCNVs on the X chromosome were identified in 33 patients (2.8%). Duplications and triplications (27 cases) were four times more common than deletions (6 cases). In 74% of patients, CNVs were of maternal origin; in 10% they were of paternal origin; and in 16% they arose de novo. The frequency of skewed X inactivation among family members who were healthy carriers of pathogenic and likely pathogenic CNVs and variants of uncertain significance (VUSs) on the X chromosome was 23%. For the first time, we reported several CNVs, including a pathogenic microdeletion at Xq26.1q26.2 involving the ARHGAP36 gene and a microduplication at Xp22.2 involving the OFD1 gene,

conclusionsThis study expands on the frequency and spectrum of CNVs in patients with NDDs. Pathogenic variants on the X chromosome were present in 15% of cases, LP in 12%, VUS in 57%, and LB in 16% of cases. Previously unreported CNVs aid in the identification of new structural variants and genes associated with X-linked intellectual disability. We propose to consider the X-chromosome inactivation status when assessing the pathogenetic significance of CNVs using the ACMG algorithm (American College of Medical Genetics).

Indexed as

ARHGAP36CNVMID1Neurodevelopmental disordersOFD1UBE2AX chromosome inactivationX-linked intellectual disability

Identifiers

PMID39985054
PMCPMC11846235

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