We aim to collect skin and blood cells from two to three WitKoS patients, reprogram these cells into iPSCs and use the iPSCs for differentiation into neurons/neural organoids to study the molecular underpinnings of WitKoS.
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the differences in cell morphology, tissue
architecture, transcriptomic profile and cellular function between patient and
healthy control derived organoids.
Secondary outcome
- Study the effect of medication on WitKoS patient-derived iPSC based models.
- Study whether iPSCs derived from blood will form neural organoids equally
well compared to organoids from skin cell derived iPSC lines.
Background summary
Witteveen-Kolk syndrome (WitKoS), a neurodevelopmental disorder (NDD), is
caused by mutations in the SIN3A gene. The underlying mechanism by which
mutations in SIN3A cause abnormalities in brain development and result in NDD
is poorly understood. Induced pluripotent stem cells (iPSCs), derived from
patients* biomaterial, provide us with a unique opportunity to study the
underlying molecular mechanisms in relevant human cell types, such as neurons
or neural tissue. Advancing the molecular understanding of WitKoS is required
to understand disease variability and to be able to develop syndrome-specific
therapies in the future.
Study objective
We aim to collect skin and blood cells from two to three WitKoS patients,
reprogram these cells into iPSCs and use the iPSCs for differentiation into
neurons/neural organoids to study the molecular underpinnings of WitKoS.
Study design
Laboratory study, using patient-specific skin cells and blood for the
generation of iPSCs and subsequently for neurons/neural organoids
Study burden and risks
This study can only be carried out in individuals with neurodevelopmental
problems (NDD), since SIN3A causes NDD when mutated. WitKoS is very rare and
generally only diagnosed in individuals that are young and/or have
neurocognitive problems. Therefore including subjects with NDD is inherent to
the study question. The results of this study will contribute to an increase in
knowledge and understanding of the underlying mechanisms in WitKoS.
Subjects will be asked to give a one-time blood sample (2x10ml) - which can
result in pain at the site of venapuncture and/ or hematoma - and a skin biopsy
- which can leave a small scar. The collection of these materials for the
generation of iPSCs and their subsequent use for neuronal cell culture models
has a minimal risk for adverse events and/or unsolicited findings, which will
be clearly communicated to the participants in the recruitment phase
Geert Grooteplein 10
Nijmegen 6500 HB
NL
Geert Grooteplein 10
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
- Written informed consent to participate in this study
- Having a (likely) pathogenic variant in SIN3A
- Clinical diagnosis of WitKoS as judged by the principal investigator
- Age >= 18 years
Exclusion criteria
- Subjects who do not meet the inclusion criteria
- Subjects with another genetic variant (e.g. copy number variation, single
nucleotide variant) that most likely contributes to the neurodevelopmental
phenotype.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83902.091.23 |