Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.5
2.8
Journals
Genes
Special Issues
Molecular Genetics of Neurodevelopmental Disorders: 2nd Edition
Due to scheduled maintenance work on our servers, there may be short service disruptions on this website between 11:00 and 12:00 CEST on March 28th.
share announcement

Molecular Genetics of Neurodevelopmental Disorders: 2nd Edition

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (25 January 2026) | Viewed by 3572

Special Issue Editors

Prof. Dr. Richard Eugene Frye

E-Mail Website
Guest Editor
Autism Discovery and Treatment Foundation and Rossignol Medical Center, Phoenix, AZ, USA
Interests: neurodevelopmental disorders; metabolic disorders; genetic symptoms; epigenetics; gene regulation
Special Issues, Collections and Topics in MDPI journals
Dr. Richard Boles

E-Mail Website
Guest Editor
Mitochondrial and Molecular Medicine, 630 S Raymond Avenue, Unit 310, Pasadena, CA 91105, USA
Interests: mitochondrial medicine; functional disease (including cyclic vomiting syndrome, other atypical forms of migraine, and chronic fatigue syndrome); autism spectrum disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Following the success of our first edition, we are delighted to present the second edition of this Special Issue, continuing our exploration of neurodevelopmental disorders—a group of conditions that profoundly impact children during critical developmental periods, with lifelong consequences for them and their families. Despite significant research, key questions remain regarding the etiology of these disorders. While genetic factors play a key role and numerous risk variants are known, the mechanisms linking these variants to autism phenotypes—as well as how interventions might alter developmental trajectories—are still unclear.

This second edition aims to publish high-impact, cutting-edge articles on emerging developments in complex genetic processes and/or gene–environmental interactions, which can provide insight into the pathophysiological processes that underlie the etiology or pathophysiology of neurodevelopmental disorders.

We encourage the submission of manuscripts describing any of the above-listed factors that provide insight into the etiological or pathophysiological processes underlying neurodevelopmental disorders. Research that enhances the description of genetic variants or conditions and elucidates underlying biological mechanisms and concepts that translate into novel treatments is also encouraged but not required.

Manuscripts will be considered that describe any genetic processes or genetic syndromes involved in the development of neurodevelopmental disorders.

Prof. Dr. Richard Eugene Frye
Dr. Richard Boles
Guest Editors

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. Genes 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 2600 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
  • attention deficit hyperactivity disorder
  • intellectual disabilities
  • autism spectrum disorder
  • mitochondria
  • neuroinflammation
  • epigenetics
  • transcriptomics
  • genetic syndromes
  • polygenetic interactions

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 (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

11 pages, 709 KB  
Article
Complexity of Inheritance of Pathogenic Mutations Associated with Epilepsy in Consanguine Families from Pakistan
by Khajista Tahira, Anwar Ullah, Fazl Ullah, Jeena Aziz, Muhammad Ishaq Javed, Aasma Kiyani, Azra Khanum, Kerstin Hallmann, Tobias Baumgartner, Rainer Surges, Pakeeza Arzoo Shaiq and Wolfram S. Kunz
Genes 2026, 17(2), 157; https://doi.org/10.3390/genes17020157 - 29 Jan 2026
Viewed by 397
Abstract
Background/Objectives: Consanguine families are helpful to identify recessive candidate genes for inherited diseases, but can also show an unusual inheritance pattern of pathogenic mutations. In this case series, we demonstrate this in five consanguine families with epilepsy from Pakistan. Methods: We [...] Read more.
Background/Objectives: Consanguine families are helpful to identify recessive candidate genes for inherited diseases, but can also show an unusual inheritance pattern of pathogenic mutations. In this case series, we demonstrate this in five consanguine families with epilepsy from Pakistan. Methods: We performed whole exome sequencing of respective index patients, analyzed the data using two different models for inheritance of mutations and determined the segregation pattern of relevant mutations in the families by bi-directional Sanger sequencing. Results: Apart from mutations in classical dominant epilepsy genes (TSC2, DEPDC5, and CACNA1I), pathogenic mutations in rare recessive epilepsy-related genes (PGAP2, NOVA2, and CCDC88C) were also identified. Interestingly, we were able to provide evidence that GALR2 is potentially an additional gene associated with a recessive form of epilepsy. In one family, a homozygous ‘pathogenic’ TRAF3IP1 p. Gly387* nonsense mutation was identified, which, most probably due to stop-codon read-through, did not contribute to the phenotype. Conclusions: Our case series of consanguine families with epilepsy exemplifies the inheritance pattern of mutations in rare recessive epilepsy genes, and shows that mutations in classical epilepsy genes showing dominant or sporadic inheritance can also be relevant. That requires the analysis of whole exome data on the basis of different inheritance models. Full article
(This article belongs to the Special Issue Molecular Genetics of Neurodevelopmental Disorders: 2nd Edition)
►▼ Show Figures

Figure 1

15 pages, 292 KB  
Article
Adaptive and Behavioral Phenotype in Pediatric 22q11.2 Deletion Syndrome: Characterizing a High-Risk Neurogenetic Copy Number Variant
by Larissa Salustiano Evangelista Pimenta, Claudia Berlim de Mello, Guilherme V. Polanczyk, Leslie Domenici Kulikowski, Maria Isabel Melaragno and Chong Ae Kim
Genes 2026, 17(2), 120; https://doi.org/10.3390/genes17020120 - 24 Jan 2026
Viewed by 423
Abstract
22q11.2 deletion syndrome (22q11.2DS) is the most common recurrent microdeletion in humans and a prototypical high-risk neurogenetic copy number variant (CNV) associated with a broad spectrum of neurodevelopmental and psychiatric disorders, including intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), anxiety, [...] Read more.
22q11.2 deletion syndrome (22q11.2DS) is the most common recurrent microdeletion in humans and a prototypical high-risk neurogenetic copy number variant (CNV) associated with a broad spectrum of neurodevelopmental and psychiatric disorders, including intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), anxiety, and psychotic symptoms. This hemizygous deletion encompasses multiple genes involved in brain development and neural circuit function, contributing to marked phenotypic variability and multisystem involvement. In pediatric populations, deficits in adaptive functioning are frequently reported and may occur independently of global intellectual impairment, reflecting broader behavioral vulnerabilities within this genetic risk architecture. Background/Objectives: This study aimed to characterize the sociodemographic, clinical, and intellectual profiles of children and adolescents with 22q11.2DS and to examine adaptive functioning and its associations with behavioral difficulties. Methods: Thirty-four patients aged 1–17 years with a confirmed molecular diagnosis of 22q11.2DS were assessed. Standardized instruments were used to evaluate cognitive performance, adaptive functioning, and behavioral outcomes. Results: Intellectual disability was highly prevalent, with most participants showing combined cognitive and adaptive impairments. Adaptive functioning was compromised across domains, with relatively higher socialization scores compared to other areas, such as daily living skills. Multivariate analyses indicated associations between sociodemographic factors and behavioral difficulties, as well as between social problems and lower global adaptive functioning. Conclusions: Together, these findings contribute to the characterization of the adaptive and behavioral phenotype associated with a high-risk neurogenetic CNV and highlight the relevance of adaptive functioning as a key outcome for early evaluation and intervention in pediatric 22q11.2DS. Full article
(This article belongs to the Special Issue Molecular Genetics of Neurodevelopmental Disorders: 2nd Edition)
36 pages, 369 KB  
Article
De Novo Variants Predominate in Autism Spectrum Disorder
by Richard G. Boles, Omri Bar, Philip T. Boles, Zoë R. Hill and Richard E. Frye
Genes 2025, 16(9), 1099; https://doi.org/10.3390/genes16091099 - 17 Sep 2025
Cited by 2 | Viewed by 2297
Abstract
Background: Autism spectrum disorder (ASD) is a common condition with substantial personal and financial burdens of lifelong implication. Multiple twin studies have confirmed a genetic or inherited component at ~80%, higher than any other common condition. However, ASD’s rapidly accelerating prevalence, now at [...] Read more.
Background: Autism spectrum disorder (ASD) is a common condition with substantial personal and financial burdens of lifelong implication. Multiple twin studies have confirmed a genetic or inherited component at ~80%, higher than any other common condition. However, ASD’s rapidly accelerating prevalence, now at 1 in 31 in the USA, appears to defy a predominantly genetic basis and implicate our rapidly changing environment. A potential explanation for this paradox is a recent increase in de novo variants (DNVs), which are “new” mutations present in the patient yet absent in both parents. The present authors recently reported using trio whole-genome sequencing (trio-WGS) that DNVs highly likely to be highly disease-associated (“Principal Diagnostic Variants”, PDVs), mostly missense variants, were present in (25/50) 50% of the ASD patients clinically evaluated by our team. Methods: The current study was designed to support this observation with trio-WGS in 100 additional unrelated ASD patients. Results: De novo PDVs were identified in 47/100 (47%) of cases, in close approximation to our previous work. Using non-transcribed (up and downstream) variants for all genes as a control group, these DNV-PDVs were far more likely (p < 0.0001, OR 5.8, 95% C.I. 2.9–11) to be in SFARI-listed genes associated with ASD. Consistent with the emerging polygenic model, using the same analyses, inherited missense variants were also associated with ASD (p < 0.0001). Highly unexpectedly, silent variants, both inherited (p < 0.0001) and de novo (p < 0.007), were also statistically associated with ASD, and, among inherited variants, silent variants were more associated with ASD than were missense variants (p < 0.0001). Adding silent DNVs as PDVs increases the proportion of our subjects with at least one DNV-PDV to 55% of the subjects. Conclusions: Our proposed model for ASD, with prominent DNVs in most that are genetic yet not inherited, predicts the known predominant genetic pathogenesis and the accelerating prevalence of ASD, possibly from environmental factors, including insufficient nutrients and toxicant exposures, and/or the disrupted folate metabolism known to be associated with ASD. Limitations to this study include predominant inclusion of severely affected individuals and the lack of an unaffected control group and functional validation of variant pathogenicity. Full article
(This article belongs to the Special Issue Molecular Genetics of Neurodevelopmental Disorders: 2nd Edition)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop