Research
Advancing ZTTK Research
The ZTTK SON-Shine Foundation is building the research infrastructure and partnerships needed to elucidate the molecular mechanisms underlying ZTTK syndrome and accelerate therapeutic development.
We have built a growing research toolbox that includes patient cell lines and biosamples, animal models, electronic health records, caregiver-reported data, and more. Together, these resources are designed to enable researchers to investigate ZTTK biology, identify biomarkers and therapeutic targets, and develop and test potential treatments.
We support our existing research partners and are actively seeking new investigators and collaborators who can bring additional expertise and innovative ideas to ZTTK research.
Interested in collaborating? Please contact Dr. Mara Cowen at mcowen@zttk.org to discuss research opportunities.
Join our ZTTK Researcher Listserv to stay connected with research opportunities, available resources, funding announcements, and updates from the ZTTK research community.
The SON Gene
Also known as NREBP, BASS1, Protein DBP-5, SON3. Located on chromosome 21 (21q22.11), spanning 34,463 bp with 12 regular exons. Canonical protein isoform: 2,426 amino acids. Ubiquitously expressed in all human tissues and all brain cell types.
RNA Splicing & Gene Transcription
SON is a critical splicing factor required for intron removal, cassette exon inclusion, and correct splicing of weak splice sites. It also plays an inhibitory role in transcription via menin interaction and H3K4Me3 repression.
Nuclear Speckle Formation
SON forms the core of nuclear speckles with SRRM2. Knockdown causes changes in cell morphology, defective microtubule dynamics, DNA double-strand breaks, and disrupted cell-cycle progression.
Ciliogenesis
SON is associated with centriole formation and cilia assembly. Dysfunction contributes to poor ciliogenesis — linking ZTTK to other ciliopathies.
Natural History & Phenotypic Spectrum
SON is ubiquitously expressed in all human tissues and all brain cell types. The foundation supports natural history studies to characterize how ZTTK changes over time across diverse patient populations.
Model Systems
The foundation is building shared research infrastructure available to investigators globally.
iPSC Cell Models
The world's first ZTTK induced pluripotent stem cells with isogenic controls are in development in the Ahn lab. These will be deposited in biobanks for access by any researcher globally.
Mouse Models
A haploinsufficient ZTTK mouse model has been developed by the Ahn lab. Additional models are in progress in partnership with The Jackson Laboratory (JAX), supporting evaluation of SON haploinsufficiency across organ development and hematopoiesis.
Active Research Programs
All foundation-funded research operates under a no-indirect-cost policy — 100% of grant awards go directly to the science.
iPSC Cell Models
World-first ZTTK stem cells with isogenic controls in development. Will be deposited in biobanks for access by any researcher globally.
Mouse Models
Haploinsufficient ZTTK mouse developed by the Ahn lab. Additional models in progress in partnership with The Jackson Laboratory (JAX).
Neuron Differentiation
Turning patient iPSCs into glutamatergic neurons to characterize differences in RNA expression, morphology, and synaptic signaling.
Small Molecule Screening
Active screening program evaluating repurposed compounds for therapeutic potential in ZTTK syndrome.
Gene Therapy Exploration
Exploring gene replacement therapy, antisense oligonucleotide (ASO), and gene-modulating approaches.
Care Recommendations Manual
Developing physician guidance in collaboration with the Clinical Advisory Board. GeneReview chapter for clinical reference also in development.
Key Publications
Dingemans et al.
Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON
Most complete patient dataset — 52 individuals
View publication →Kim et al.
De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome
Led by Dr. Erin Ahn — foundational discovery paper (2016)
View publication →Vukadin et al.
A mouse model of Zhu-Tokita-Takenouchi-Kim syndrome reveals indispensable SON functions in organ development and hematopoiesis
ZTTK mouse model
View publication →Stemm-Wolf et al.
The SON RNA splicing factor is required for intracellular trafficking structures that promote centriole assembly and ciliogenesis
ZTTK in relation to other ciliopathies
View publication →Halliday et al.
Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome
Expanding dataset of ZTTK MRI findings
View publication →Full publication list and collaboration inquiries: eyahn@uabmc.edu (Dr. Erin Ahn) or mcowen@zttk.org (Dr. Mara Cowen, Scientific Director)
Patient Data Access
The foundation maintains a global contact registry and partners with two patient data platforms that support natural history studies and clinical trial design:
- Citizen Health — US families; retrieves data across all providers and points of care (~5 min enrollment)
- Rare-X — US + international; multilingual (English, French, Spanish, Portuguese); longitudinal surveys + genetic report uploads (~20 min initial enrollment)
Contact the Foundation to discuss researcher data access.
Research Contacts
Collaborate With Us
The foundation is actively seeking researchers interested in studying ZTTK syndrome, the SON gene, or related neurodevelopmental pathways. We provide funding, patient connections, and access to model systems.
Contact the Foundation