Science AI Journal
Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Genetics and Neurodevelopmental Disorders

342 gap statements mined from Genetics and Neurodevelopmental Disorders papers in our 7.9M-paper local library, which holds 1,384 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

Choosing where to publish on Genetics and Neurodevelopmental Disorders? See the ranked Biology journals.

What the literature leaves open

  • There is a need for a more detailed understanding of the developmental trajectories in 15q13.3-deletion cortical organoids. Prior studies have not fully addressed the overlap between these trajectories and RA-related expression programs. The distinctiveness of the gene sets used in these studies is also not well understood.

    Exploratory donor-aware analysis of developmental transcriptomic trajectories in 15q13.3-deletion cortical organoids · 2026 · DOI

  • The need to control for variables such as age, sex, and genetic background in the mouse model.

    Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice · 2025 · DOI

  • Neurodevelopmental disorders (NDDs) are highly polygenic, yet the functional consequences of most associated non-coding variants remain unclear.

    Systematic Functional Interrogation of Neurodevelopmental Disorder Risk Variants · 2026 · DOI

  • Loss of CDKL5 leads to altered synapse development, excitatory-inhibitory imbalances and glial changes, but the underlying molecular mechanisms remain incompletely understood, particularly at the level of individual brain cell subtypes.

    CDKL5 deficiency alters cell subtype-specific molecular programmes and intercellular signalling in the mouse hippocampus · 2026 · DOI

  • Although the genetic mechanisms underlying these disorders are well established, the contribution of glucocorticoid signaling pathways and neuroendocrine regulation remains unclear.

    Cortisol homeostasis and glucocorticoid signaling are altered in FMR1 full mutation and premutation carriers. · 2026 · DOI

  • Besides severe symptoms such as profound intellectual disability, loss of speech and motor skills and epilepsy, loss of function of MECP2 has been associated with pubertal dysregulation, but the biological mechanisms leading to this remain unclear.

    Pubertal development and hypothalamic–pituitary–gonadal axis are altered in male mice lacking Mecp2 · 2026 · DOI

  • Despite an increasing number of reported cases, RLIM‐associated disorders remain underdiagnosed and poorly understood, with no cure or targeted treatments, largely due to limited insight into the cellular and molecular mechanisms underlying their pathogenesis.

    RLIM ‐associated neurodevelopmental disorders: From clinical spectrum to molecular mechanisms · 2026 · DOI

  • Finally, we discuss the key open questions that must be addressed to achieve a comprehensive cellular and molecular understanding of RLIM‐associated disorders and thus lay the foundation for future therapeutic interventions.

    RLIM ‐associated neurodevelopmental disorders: From clinical spectrum to molecular mechanisms · 2026 · DOI

  • To our knowledge, neurodevelopmental regression has not been documented in confirmed NEDHIB cases, and no standardized therapeutic regimens are established for clinical management.

    De novo POLR2A p.(L1127F) variant presenting with neurodevelopmental regression and dystonia, with favorable response to low-dose dopamine therapy: a case report and literature review · 2026 · DOI

  • However, comprehensive clinical descriptions of individuals with pathogenic BRSK2 variants remain limited, and the molecular and cellular consequences of these mutations are poorly understood.

    Catatonia and regression in an autism spectrum disorder patient harbouring a BRSK2 frameshift mutation · 2025 · DOI

  • Furthermore, this report demonstrates the role of BRSK2 in complex neuropsychiatric features—such as catatonia and cognitive deterioration, which remain underreported in the existing literature—and emphasises the importance of longitudinal cognitive and behavioural monitoring in individuals with BRSK2 mutations.

    Catatonia and regression in an autism spectrum disorder patient harbouring a BRSK2 frameshift mutation · 2025 · DOI

  • Previous studies have focused on the effect of the PURA variant in the cytoplasmic location, but nuclear mislocalisation remains to be explored.

    PURA protein mislocalisation in the nucleus: mechanistic basis for transcriptional dysregulation and DNA unwinding deficits in a model of the p.L148Wfs*77 PURA variant · 2025 · DOI

  • Despite recent advances to elucidate GRD pathophysiological mechanisms and to find treatments, to date, GRD therapeutic arms are still scarce and with limited efficacy.

    Spermidine Treatment Improves GRIN2B Loss‐Of‐Function, A Primary Disorder of Glutamatergic Neurotransmission · 2025 · DOI

  • However, the molecular mechanisms by which early social isolation affects prefrontal PV neurons causing social impairments remain unclear.

    Npas4 drives the effects of early social isolation on social behaviors and prefrontal parvalbumin neurons · 2025 · DOI

  • Myelin transcription factor 1 like (MYT1L) is a neuronal transcription factor highly expressed in the developing and adult brain, and, while pathogenic MYT1L mutations cause neurodevelopmental disorders, these have not been characterized in human models of neurodevelopment.

    Autism- and intellectual disability-associated MYT1L mutation alters human cortical interneuron differentiation, maturation, and physiology · 2025 · DOI

  • Auditory hypersensitivity is a well-established phenotype of Fragile X syndrome (FXS), but how it relates to neurobehavioral biomarkers remains poorly understood.

    Hyper-extralemniscal model of Fragile X syndrome · 2025 · DOI

  • Communication has not been systematically examined to guide intervention recommendations.

    Expanding the phenotype of Kleefstra syndrome: speech, language and cognition in 103 individuals · 2024 · DOI

  • Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to the POGZ-associated syndrome remain unclear.

    Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder · 2024 · DOI

  • The study highlights the need to investigate the impact of early-life stress on FXS-related neuropathology.

    Fmr1 Deletion and Early-Life Stress Interact to Increase Cell Proliferation and Glial Populations at the Expense of Immature Neurons in the Adult Dentate Gyrus · 2026 · DOI

  • Rett syndrome arises from loss-of-function mutations in the X-linked chromatin regulator MECP2, yet the earliest molecular derailments in development are poorly defined.

    MECP2 mutations rewire human ESC fate and bias cortical lineage commitment · 2026 · DOI

  • Sex-specific predilection in neurological diseases caused by mutations in autosomal genes is a phenomenon whose molecular basis is poorly understood.

    ZNF142 mutation causes sex-dependent neurologic disorder · 2024 · DOI

  • The Polycomb Repressive Complex 2 (PRC2) regulates corticogenesis, yet the consequences of mutations to this epigenetic modifier in the mature brain are poorly defined.

    Polycomb repressive complex 2 is critical for mouse cortical glutamatergic neuron development · 2024 · DOI

  • For quick reference, a summary of the major recommendations from this section, stratified by variants and clinical context is provided (box 1). Criteria for genetic testing of RYR1 Suspected clinical diagnosis of malignant hyperthermia.

    EMQN Best Practice Guidelines for Genetic Testing and Reporting in RYR1-related disorders · 2026 · DOI

  • Leave-one-deletiondonor-out analyses assessed dependence on each affected donor, - mixed-effects models were fitted as sensitivity analyses, - gene-set distinctiveness, not RA specificity, should be evaluated in future…

    Exploratory donor-aware analysis of developmental transcriptomic trajectories in 15q13.3-deletion cortical organoids · 2026 · DOI

  • The study only used a mouse model, - The sample size was limited to 6 mice per group, - The study only examined the MECII…

    Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice · 2025 · DOI

Most-cited papers in Genetics and Neurodevelopmental Disorders

Most recent work

Find a gap in your own Genetics and Neurodevelopmental Disorders sub-topic

This page shows what the Genetics and Neurodevelopmental Disorders literature already flags as unresolved. To narrow it to your specific question, search the Research Gap Finder: the search is free with a free account and lists the papers closest to your topic first. Unlocking that topic (50 credits, charged once) fills the comparison table from our 7.9M-paper local library and writes the gaps from its rows.

Open the Research Gap Finder →

Related topics in Biochemistry, Genetics and Molecular Biology

Gut microbiota and health
4,284 open questions
Extracellular vesicles in disease
1,862 open questions
Antibiotic Resistance in Bacteria
1,778 open questions
Inflammatory Bowel Disease
1,518 open questions
RNA modifications and cancer
1,209 open questions
Single-cell and spatial transcriptomics
1,178 open questions
Genetic Associations and Epidemiology
1,146 open questions
Epigenetics and DNA Methylation
1,090 open questions
Open questions raised by papers listed on this page include: (1) There is a need for a more detailed understanding of the developmental trajectories in 15q13.3-deletion cortical organoids (“Exploratory donor-aware analysis of developmental transcriptomic trajectories…”, 2026); (2) Neurodevelopmental disorders (NDDs) are highly polygenic, yet the functional consequences of most associated non-coding variants remain unclear (“Systematic Functional Interrogation of Neurodevelopmental Disorder Risk Variants”, 2026); (3) Loss of CDKL5 leads to altered synapse development, excitatory-inhibitory imbalances and glial changes, but the underlying molecular mechanisms remain incompletely understood, particularly at the level of individual brain cell subtypes (“CDKL5 deficiency alters cell subtype-specific molecular programmes and…”, 2026); (4) Although the genetic mechanisms underlying these disorders are well established, the contribution of glucocorticoid signaling pathways and neuroendocrine regulation remains unclear (“Cortisol homeostasis and glucocorticoid signaling are altered in FMR1 full…”, 2026); (5) Comprehensive clinical descriptions of individuals with pathogenic BRSK2 variants remain limited, and the molecular and cellular consequences of these mutations are poorly understood (“Catatonia and regression in an autism spectrum disorder patient harbouring a…”, 2025). 342 gap statements have been mined from Genetics and Neurodevelopmental Disorders papers in our 7.9M-paper local library, which holds 1,384 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

Tools for your next paper

Gaps & Literature SearchFind open questions in any field — 1,100,000+ open gaps mined from our own library.Pre-CheckIs your paper ready? Acceptance odds for top, mid and open/emerging journals, in seconds.Journal FinderA ranked shortlist of target journals from a 17,500-venue index.Duplicate Publication CheckerCheck for prior publication across 7 sources and our local library.Citation GeneratorFreeA DOI or title → APA, MLA, Vancouver, Chicago, BibTeX, RIS. No signup.Graphical Abstract MakerFreeTurn your findings into a colorblind-safe graphical abstract.

How Pre-Check worksHow AI Review works

Compare the category — Honest roundups of the AI research tools, ours listed alongside the alternatives.

Command palette

Jump anywhere, run any action.