213+ patient cell lines across 15 rare disease genotypes. Our core focus is chromosome 15q imprinting disorders — the most underserved category in pediatric rare disease neurology.
Duplication 15q syndrome (Dup15q) results from extra copies of the 15q11-q13 chromosomal region — the most frequent chromosomal cause of autism spectrum disorder. The duplicated region contains several imprinted genes, including UBE3A, which is expressed exclusively from the maternal allele in neurons.
Depending on copy number and origin (maternal isodicentric vs. interstitial duplication), children with Dup15q present with intellectual disability, hypotonia, autism, and treatment-resistant epilepsy. Seizure onset often occurs in the first year of life.
Our DPSC neuronal models demonstrate significant transcriptional differences in Dup15q neurons compared to controls and to Angelman syndrome deletion neurons — revealing disease-specific molecular signatures that are not apparent from genetics alone.
Key reference: Urraca N et al. (2018). Molecular Autism. PMID: 29423132
Angelman syndrome (AS) results from loss of maternally-expressed UBE3A function in neurons. The most common cause is maternal deletion of 15q11-q13 (~65–70%), with the remainder due to paternal uniparental disomy, imprinting defects, or UBE3A point mutations.
Clinically, AS is characterized by severe intellectual disability, absent speech, ataxia, seizures (present in >90%), and a happy, sociable demeanor. It is one of the most severe imprinting disorders, with no approved disease-modifying treatment as of 2026.
The silenced paternal UBE3A allele is an attractive therapeutic target. Our DPSC neuronal platform supports both ASO-based unsilencing strategies (developed by multiple groups targeting the UBE3A antisense transcript) and CRISPR-Cas9 based correction approaches — tested directly in patient-matched neuronal cells.
Our lab also identified PIEZO2 mechanosensory channel dysfunction in an Angelman mouse model, revealing a new molecular phenotype relevant to the sensory abnormalities seen in patients. Nat Commun 2023.
Prader-Willi syndrome (PWS) results from loss of paternally-expressed genes in the 15q11-q13 region — the mirror image of Angelman syndrome. Causes include paternal deletion (~70%), maternal uniparental disomy (UPD, ~25%), and imprinting defects (~3%).
PWS presents with neonatal hypotonia and feeding difficulties, followed by hyperphagia and obesity, intellectual disability, behavioral problems, and in many cases autism spectrum disorder — with UPD cases showing higher rates of ASD than deletion cases.
Our 2021 Frontiers in Molecular Neuroscience paper revealed decreased mitochondrial volume specifically in UPD+ASD PWS neurons, providing a cellular mechanism for increased autism susceptibility in this genotype. Our 2025 HGG Advances paper identified circadian rhythm defects — two distinct period length phenotypes — in PWS DPSC neurons, opening new therapeutic avenues targeting the molecular clock.
Schaaf-Yang syndrome (SYS) is caused by truncating variants in the paternally expressed copy of MAGEL2, an imprinted gene within the Prader-Willi critical region on chromosome 15q11-q13. About half of cases are inherited from an unaffected carrier father; the rest arise de novo.
SYS overlaps clinically with Prader-Willi syndrome — neonatal hypotonia, feeding difficulties, and developmental delay — but is distinguished by joint contractures and a much higher rate of autism spectrum disorder, which affects roughly 75–80% of individuals.
Because MAGEL2 is one of the genes lost in PWS, SYS neurons let us isolate the contribution of a single 15q imprinted gene to neuronal phenotypes. Our lab co-authored a 2020 JCI Insight study showing that loss of MAGEL2 reduces secretory granule abundance and neuropeptide production. SYS is an active project at PulpNeuro, building directly on our PWS neuron work.
Key reference: Chen H et al. (2020). JCI Insight. PMID: 32879135
Congenital central hypoventilation syndrome (CCHS) is a disorder of autonomic control caused by variants in PHOX2B, a transcription factor essential for development of the autonomic nervous system from the neural crest. Inheritance is autosomal dominant, and more than 90% of cases arise from new variants.
Children with CCHS do not breathe adequately on their own, especially during sleep, and many require lifelong ventilatory support. Heart rate, blood pressure, and temperature regulation can also be affected; about 20% of individuals have Hirschsprung disease, and there is an increased risk of neural crest tumors such as neuroblastoma.
Because DPSC are themselves neural crest-derived, they are a natural model for PHOX2B-driven disease. Our 2023 Frontiers in Pediatrics study compared DPSC-derived neurons from CCHS, ROHHAD, and PWS patients and found shared transcriptional changes between CCHS and ROHHAD, including altered ADORA2A expression validated at the protein level. A second CCHS paper is currently in revision.
Key reference: Victor AK et al. (2023). Frontiers in Pediatrics 11:1090084. PMID: 37234859
WAGR syndrome is a contiguous gene deletion disorder caused by loss of chromosome 11p13. It is named for its main features: Wilms tumor, aniridia, genitourinary anomalies, and a range of developmental delays and intellectual disability. WT1 and PAX6 are deleted in all individuals with typical WAGR.
Deletion size varies between individuals. When the deletion extends to include BDNF (WAGRO syndrome), children develop childhood-onset obesity and may have a greater risk of intellectual disability and autism. WAGR affects an estimated 1 in 500,000 to 1 in 1 million people.
Variable deletion boundaries make WAGR a powerful natural experiment: comparing DPSC-derived neurons from individuals with and without BDNF loss can separate the neuronal effects of individual genes in the region.
In an active collaboration with Ryosuke Sato, Ph.D. (Department of Physiology, Tulane University School of Medicine), we are developing kidney organoids from WAGR patient DPSC. These patient-specific organoids will allow us to identify the molecular cause of Wilms tumor in this disorder, a question that has been difficult to study without human kidney tissue carrying the patient's own 11p13 deletion.
Because DPSC come directly from a child's shed baby tooth — collected at home and mailed by parents — we can generate neurons from any individual with any rare neurogenetic variant, anywhere in the world.
This creates a true precision medicine approach: test ASO efficacy in the patient's own genetic background before committing to a clinical approach. Tune drug pharmacology to that patient's specific receptor variants. Validate CRISPR guide RNA efficiency in patient-matched neurons before any human use. Essentially, our cells can fill the pre-clinical gap between mouse models and clinical trials in actual patient neurons.
For ultra-rare diseases affecting only tens or hundreds of patients worldwide, the n=1 model isn't just an aspiration — it's the only viable path to personalized treatment. Our platform makes it practical.
Patient ships shed baby tooth from anywhere in the world
DPSC neurons generated in patient-specific genetic background
ASO, small molecule, or CRISPR validation in that patient's own neurons
| Disorder | Cell Lines |
|---|---|
| Neurotypical Control | 36 |
| Duplication 15q | 36 |
| Prader-Willi Syndrome | 46 |
| Angelman Syndrome | 23 |
| Tuberous Sclerosis | 22 |
| WAGR Syndrome | 10 |
| Smith-Magenis Syndrome | 7 |
| Schaaf-Yang Syndrome | 6 |
| CCHS | 6 |
| 22q Deletion Syndrome | 6 |
| Potocki-Lupski / PTLS | 8 |
| DDX3X Syndrome | 3 |
| USP7 | 2 |
| ATRX Syndrome | 1 |
| Smith-Lemli-Opitz Syndrome | 1 |
| Total | 213+ |
Cell library continues to grow. Contact us to discuss specific genotypes or custom collection arrangements.