Our main goal is to develop an in vitro model to investigate the function of wildtype and mutant KDM2B in neuronal development. We want to use this model to investigate genotype-phenotype correlations, elucidate isoform expression in neuronal…
ID
Source
Brief title
Condition
- Neurological disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
This is a fundamental research study without clear defined end-points where we
aim to develop an in vitro cell model of the KDM2B syndrome.
Secondary outcome
Inclusion of 15 patients and their clinical data entered in Castor, 6 skin
biopsies, 5 successfully reprogrammed iPSC, 3 successful differentiation to
neurons, 3 generated isogenic controls.
Background summary
Recently, we delineated a novel syndrome caused by heterozygous variants in the
KDM2B gene (van Jaarsveld et al, submitted). Individuals present with
developmental delay and/or intellectual disability, autism, ADHD and congenital
organ anomalies. The role of KDM2B in human (neuro)development and the
molecular mechanisms leading to this disorder remain to be elucidated. Affected
individuals suffer lifelong from neurodevelopmental issues, and while there is
potential reversibility by targeting epigenetic changes, there is a huge
knowledge gap to be bridged rather sooner than later.
Study objective
Our main goal is to develop an in vitro model to investigate the function of
wildtype and mutant KDM2B in neuronal development. We want to use this model to
investigate genotype-phenotype correlations, elucidate isoform expression in
neuronal development and study cellular and molecular effects of KDM2B
variants. Furthermore, we want to determine clinical spectrum of KDM2B clinical
disorder in more detail.
Study design
In this study, clinical data of individuals carrying KDM2B variants is
collected (retrospective cohort study). Next to this aspect, this study
consists of fundamental research, as patient fibroblasts are collected and used
to develop an in vitro model to investigate the consequences of mutant KDM2B on
neuronal development.
Study burden and risks
The burden can be considered low since the study participation only consists of
one hospital visit and (optional) one punch skin biopsy under local anesthesia.
This procedure can leave a 3-4mm scar on the arm. This biopsy is generally
considered a safe procedure, and rare complications of skin biopsy are
relatively mild (infection, prolonged bleeding and/or hematoma of the biopsy
site).
This study could not be conducted without the participation of subjects
belonging to the group in question. This study is essential for further
research into their disorder, which is not performed elsewhere. In this way,
the outcomes can be potentially important for the subjects as well as it will
provide novel insights on the etiology of this disorder.
Huispost KC 04.084.2 Lundlaan 6
Utrecht 3584 EA
NL
Huispost KC 04.084.2 Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
Inclusion criteria
a variant in the KDM2B gene
OR having a child with a KDM2B variant who has been included in the study for
skin biopsy
Exclusion criteria
If the subject or legal caretakers are unable to provide consent
Severe bleeding disorder expected to lead to a complicated skin biopsy
Known allergy to all available local anaesthetics
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 | NL81759.041.22 |