New Insight into the Molecular Genetics of Neurodevelopmental Disorders
A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Genetics".
Deadline for manuscript submissions: 31 August 2024 | Viewed by 868
Special Issue Editors
Interests: neurodevelopment disorders (NDDs) and epilepsy; next-generation sequencing (NGS); medical genetics; molecular genetics; functional genomics
Special Issue Information
Dear Colleagues,
Neurodevelopmental disorders (NDDs) are a group of rare diseases mainly of genetic origin, resulting from abnormal brain development and characterized by impaired cognition, communication, adaptive functioning deficits, and impaired psychomotor skills. NDDs which include rare genetic syndromes, intellectual disability (ID), autism spectrum disorder (ASD) and epilepsy, have proven to be genetically and phenotypically heterogeneous raising unexpected difficulties to the phenotype-driven approach to diagnosis. The advances in genetic testing achieved through Next Generation Sequencing (NGS) have shown an enormous improvement in discovering genes associated with NDDs. However, interpreting the pathogenetic role of variants of unknown significance requires rigorous evaluation of multiple lines of evidence, including the functional effect of the variants at the protein, cellular, or model organism levels. With a better understanding of the molecular pathomechanisms and phenotypic spectra, patient management can be improved and targeted therapeutics may become more available.
This Special Issue aims to provide updates on New Insight into the Molecular Genetics of Neurodevelopmental Disorders.
We welcome Research Articles, Reviews, and Communications focused on the issue topic, including molecular, functional or animal studies modelling specific disorders and deep genotype-phenotype correlation. We look forward to your valuable contributions.
Dr. Luciana Musante
Dr. Flavio Faletra
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 100 words) can be sent to the Editorial Office for announcement on this website.
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
- next generation sequencing
- pathomechanisms
- phenotypic spectra
- phenotype-genotype correlation
Planned Papers
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: FASD and more specifically on miRNA expression modifications (buccal cells and blood samples)
Authors: Laëtitia Sennsfelder
Affiliation: Laboratoire EPI (Etudes pharmaco-immunologiques), UFR Santé, Université de La Réunion, CHU (Centre Hospitalier Universitaire) de La Réunion, 97400 Saint-Denis, France
Title: Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associate with Risk of FASD Outcomes
Authors: Leo D McKay; Berardino Petrelli; Molly TL Pind; James N Reynolds; Richard F Wintle; Albert E Chudley; Britt Drögemoeller; Abraham Fainsod; Stephen W Scherer; Ana Hanlon-Dearman; Geoffrey G. Hicks
Affiliation: University of Manitoba, Winnipeg, Canada
Abstract: Fetal Alcohol Spectrum Disorder (FASD) is a common neurodevelopmental disorder that affects an estimated 2-5% of North Americans. FASD is induced by prenatal alcohol exposure (PAE) during pregnancy and while there is a clear genetic contribution, few genetic factors are currently identified or understood. In this study, using a candidate gene approach, we performed a genetic variant analysis of retinoic acid (RA) metabolic and developmental signaling pathway genes, on whole exome sequencing data of 23 FASD diagnosed individuals. We found risk and resilience alleles in ADH and ALDH genes known to normally be involved in alcohol detoxification at the expense of causing RA deficiency, following PAE. Risk and resilience variants were also identified in RA-regulated developmental pathway genes, especially in SHH and WNT pathways. Notably we also identified significant variants in the causative genes of rare neurodevelopmental disorders sharing comorbidities with FASD, including STRA6 (Matthew-Wood), SOX9 (Campomelic Dysplasia), CDC42 and FDG1 (Aarskarog) and 22q11.2 deletion syndrome (TBX1). Although this is a small study, the findings support PAE-induced RA deficiency as a major etiology underlying FASD and suggest risk and resilience variants may be suitable biomarkers to determine the risk of FASD outcomes following PAE.
Title: immune dysregulation in Roifman Syndrome
Authors: Chaim Roifman
Affiliation: Division of Immunology & Allergy, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada.
Title: Molecular Genetics of Acquired Temporal Lobe Epilepsy
Authors: Anne-Marie Neumann; Stefan Britsch
Affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Germany
Abstract: An epilepsy diagnosis reduces a patient’s quality of life tremendously; a fate shared by over 50 million people worldwide. Temporal lobe epilepsy (TLE) was largely considered a nongenetic or acquired form of epilepsy that develops in consequence of neuronal trauma by injury, malformations, inflammation, or a prolonged (febrile) seizure. Although extensive research has been conducted to understand the process of epileptogenesis, a therapeutic approach to stop manifestation or to reliably cure the disease has yet to be developed. In this review, we briefly summarize current literature predominately based on data from excitotoxic rodent models on the cellular events proposed to drive epileptogenesis and thoroughly discuss major molecular pathways involved with a focus on neurogenesis-related processes and transcription factors. Furthermore, recent investigations emphasize the role of the genetic background for acquisition of epilepsy including variants of neurodevelopmental genes. Mutations in associated transcription factors may have the potential to innately increase vulnerability of the hippocampus to develop epilepsy following an insult – an emerging perspective on the epileptogenic process in acquired forms of epilepsy.
