Existing Research

Despite growing interest in DAND, our understanding of these syndromes remains limited. To date, only about 30 research publications—produced by a dozen research groups and centers—have focused exclusively on the DEAF1 gene. Since many fundamental scientific questions are best explored through simplified models of disease, DAND pathology has been studied using in vitro systems, human cellular models (including HEK293 cells and patient-derived organoids), and mouse models.

Cutting-edge research methods, such as recombinant DNA technology, transcriptomic analysis, and computational modeling are helping scientists close key knowledge gaps. These approaches allow researchers to better understand DEAF1’s genetic and cellular functions, the biologic pathways it influences, and the effects of DEAF1 mutations. On the clinical side, studies have primarily focused on cataloging symptoms through diagnostic imaging, behavioral assessments, clinical notes, and systems evaluations—typically with little or no direct intervention.

Key Research Articles

August 2022

Expansion and mechanistic insights into de novo DEAF1 variants in DEAF1-associated neurodevelopmental disorders

De novo DEAF1 variants in the DNA binding domain result in a spectrum of neurodevelopmental disorders through dominant-negative effects on DEAF1’s regulation of other genes.

February 2020

Impaired memory and marble burying activity in deformed epidermal autoregulatory factor 1 (Deaf1) conditional knockout mice

Conditional knockout of DEAF1 gene in a mouse model impairs memory and evokes anxiety-like behavior, associated with abnormal morphology of hippocampus.

September 2019

De novo and biallelic DEAF1 variants cause a phenotypic spectrum

A symptom analysis shows that de novo and biallelic DEAF1 variants cause a phenotypic spectrum, with intellectual disability, speech delay, motor delay, autism, sleep disturbances, and a high pain threshold characterized in both types of variants, and microcephaly exclusively observed in patients with recessive variants.

December 2018

Functional analysis of novel DEAF1 variants identified through clinical exome sequencing expands DEAF1-associated neurodevelopmental disorder (DAND) phenotype

Novel DEAF1 variants identified through clinical exome sequencing, expanding the DAND phenotype.

May 2014

DEAF1 binds unmethylated and variably spaced CpG dinucleotide motifs

DEAF1 protein binds unmethylated CpG-containing half-sites within a specific consensus sequence on DNA.

December 2014

Mutations Affecting the SAND Domain of DEAF1 Cause Intellectual Disability with Severe Speech Impairment and Behavioral Problems

Genetic mutations affecting specifically SAND domain of DEAF1 protein are associated with intellectual disability and severe speech impairment.

January 2012

Increased Serotonin-1A (5-HT1A) Autoreceptor Expression and Reduced Raphe Serotonin Levels in Deformed Epidermal Autoregulatory Factor-1 (Deaf-1) Gene Knock-out Mice

Loss of the DEAF1 gene in mice leads to increased 5-HT1A autoreceptor expression and reduced serotonin levels in brainstem. Serotonin is a neurotransmitter that regulates numerous processes, including mood, sleep, appetite, and cognition.

DEAF1 in Literature

View our “knowledge tree” of DEAF1 research, articles, and case studies. You may find your variant in literature!

Inspiring Research on Other Rare Disorders

Key DAND Milestones

  • 1996

    DEAF1 is identified as a novel DNA-binding protein, initially called NUDR (nuclear DEAF1-related) or Suppresin. [Gross et al.]

  • 2004

    2004 - DEAF1 binds both DNA and other proteins. [Jensik et al.]

  • 2008

    DEAF1 is shown to regulate immunity in fruit flies and, likely, humans. [Reed et al.]

  • 2012

    Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. [Raunch et al.]

  • 2014

    A landmark global research study and case report confirming DEAF1 as the main cause of a syndromic neurodevelopmental disorder. [Vulto-van Silfhout et al.]

  • 2019

    De novo and biallelic DEAF1 variants cause a phenotypic spectrum. [Nabais 2019]

  • 2023

    Uncovered potential mechanisms of de novo DEAF1 mutations in DAND disorders

  • 2023

    Catherine Carpenter Kahn creates the Families of DAND Facebook group

  • 2025

    The DAND Alliance is founded (launch announcement)

Current Initiatives

We are actively collaborating with scientists, clinicians, and the medical community to accelerate discoveries and drive progress in DAND research. Ongoing projects include:

Genetic and Molecular Mechanisms

Investigating how DEAF1 functions at the genetic and molecular level in vitro and in disease models.

Methylation Study

Investigating the DNA methylation in DEAF1-related disorders.

Symptom Manifestation

Mapping how DEAF1 mutations lead to specific symptoms.

Genetic Incidence and Inheritance

Studying how often DEAF1 mutations occur and their inheritance patterns using genome/exome sequencing.

Targeted Therapeutics

Exploring treatments that mitigate the effects of a mutated DEAF1 gene.

Comprehensive Care Approaches

Developing holistic treatment and support strategies for individuals and families affected by DAND.

Partner Collaborations

Partnering with groups, such as Simon’s Searchlight and Human Disease Genes to expand research efforts.

Why We’re Optimistic

We are in a new era of scientific discovery, where advances in AI-driven research and the power of patient advocacy are accelerating progress like never before. Patients, caregivers, and researchers have more tools and collaborative opportunities to drive breakthroughs and push towards meaningful treatments for those with DAND.

Innovative approaches are already in motion—from targeting the mutant part of the DEAF1 gene in vivo to testing broad-spectrum therapies on synthetic brain models. Inspired by the progress in research and treatment of other genetic conditions, we are hopeful to see a significant improvement of our loved ones’ quality of life within the next decade.