Genetic and Epigenetic Mechanisms Underlying Neurodevelopmental Disorders

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 976

Special Issue Editor


E-Mail Website
Guest Editor
Center for Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Interests: neuroimaging; inborn errors of metabolism; neurogenetics; neuroscience; neurodevelopmental disorders; genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodevelopmental disorders (NDDs) including autism spectrum disorder, intellectual disabilities, and epilepsy represent a complex interplay between genetic and epigenetic factors. While advances in genomics have revealed numerous causative variants in critical genes, growing evidence highlights a role of epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA, in modulating gene expression during brain development. This Special Issue will highlight recent breakthroughs in identifying both rare and common genetic variants, the epigenomic landscapes of early neural development, and how the environment also influences and shapes NDD risk. We encourage submissions that utilize multi-omics, animal, or organoid models and systems biology approaches to deepen our understanding of the pathogenesis of NDDs as a pathway for exploring new therapeutic targets.

Dr. Andrea L. Gropman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodevelopmental disorders
  • epigenetics
  • gene–environment interaction
  • chromatin remodeling
  • neurogenomics

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:

Research

22 pages, 368 KB  
Article
Resolving Diagnostic Uncertainty in Neurodevelopmental Disorders Using Exome Sequencing Supported by Literature-Based Multi-Omics Evidence
by Danijela Krgovic, Peter Gradisnik, Andreja Osterc Koprivsek, Ana Kogovsek, Nadja Kokalj Vokac and Spela Stangler Herodez
Biomolecules 2026, 16(3), 399; https://doi.org/10.3390/biom16030399 - 8 Mar 2026
Viewed by 635
Abstract
Background: Neurodevelopmental disorders (NDDs) are genetically heterogeneous, and exome sequencing (ES) is now a first-line diagnostic tool. However, many patients receive variants of uncertain significance (VUSs) or inherited variants with incomplete penetrance, limiting clinical interpretation. Emerging multi-omics evidence from the literature can [...] Read more.
Background: Neurodevelopmental disorders (NDDs) are genetically heterogeneous, and exome sequencing (ES) is now a first-line diagnostic tool. However, many patients receive variants of uncertain significance (VUSs) or inherited variants with incomplete penetrance, limiting clinical interpretation. Emerging multi-omics evidence from the literature can support the interpretation of novel and rare variants, helping to refine classification in selected cases. Methods: We assessed 20 patients and their parents referred for genetic testing for NDDs. ES was performed, followed by ACMG/ACGS-based variant classification, segregation analysis, and targeted literature review. Variants were included when deemed plausible contributors to the phenotype by a multidisciplinary team. Gene-level constraint metrics, in silico predictions, and emerging multi-omics evidence from the literature were integrated to support interpretation. Results: Across 18 NDD-associated genes, we identified 20 rare variants: Three pathogenic (P), nine likely pathogenic (LP), and eight VUSs. All P and most LP variants were de novo. Inherited variants, particularly in KMT5B, TANC2, SPTBN1, and CHD4, highlighted challenges related to incomplete penetrance. Two patients had dual molecular diagnoses. Several VUSs were supported by literature-derived transcriptomic, proteomic, or model-system evidence. Conclusions: This cohort underscores ongoing challenges in interpreting VUSs and inherited variants in NDDs. Integrating genomic findings with published multi-omics data enhances variant interpretation, reveals mechanistic insights, and strengthens diagnostic confidence, supporting broader adoption of multi-omics approaches in rare NDD evaluation. Full article
Back to TopTop