In order to provide the best possible care to patients with a rare disease, it is essential that knowledge about the disease is gathered worldwide. In order to stimulate care for rare diseases and the gathering of knowledge, national centers of expertise have been set up. For the formal recognition of a center of expertise by the Ministry of Health, Welfare and Sport, an important condition is that the center of expertise collects, analyses and shares knowledge by means of publications. These can be publications in scientific journals, but also treatment guidelines for doctors or information brochures for patients or caregivers. Through standardized follow-up and close cooperation between doctors and researchers, we optimize care and research within ENCORE. In this way, we can ultimately develop better treatments for rare diseases. You may therefore be asked to participate in research. Participation in research is always voluntary. The data obtained is stored and analyzed in an anonymous form. All research is approved in advance by an ethical review committee.
All patients with a chromatinopathy seen in our expertise center have already undergone genetic research (elsewhere), so this will not be done again. The outcome of this research helps us to better understand the effect of the DNA change ('mutation') on the severity of the symptoms. In rare cases, the genetic change is not unambiguous, and will be further investigated in the laboratory (see pre-clinical research).
Detailed knowledge about the course of chromatinopathies (which symptoms and complaints are there, and when exactly do they arise) is of great importance in order to be able to recognize complaints early in the future and to treat them optimally. In addition, this is important for drug research (trials). After all, only if we can demonstrate that a new drug improves the quality of life will the drug actually be approved and reimbursed by the insurer.
Because chromatinopathies are a relatively new group of disorders, we do not yet have sufficient insight into the most important clinical characteristics and how they develop over time. The chromatinopathies consultation hour of the ENCORE Expertise Center is intended to provide an overview of this. We hope, if the center has sufficient capacity, to also be able to see patients with a chromatinopathy within the pediatric brain lab (Child brain center). Here the function and development of children with a brain disorder are tested, in an appealing circuit and in a child-friendly manner.
A patient day, such as the Kleefstra Syndrome day for families and patients organized last year, can also contribute to improving information and treatments. The goal is to eventually map the natural course (the “Natural History”) of many chromatinopathies. This could, for example, create a (worldwide) patient registry in which data on genetic mutations and associated symptoms (so-called phenotype-genotype correlations) can be recorded, with which the severity of the disease can be predicted based on the mutation found.
Draksler et al. (2024) Exploring Kleefstra syndrome cohort phenotyp characteristics: Prevalence insights from caregiver-reported outcomes Eur J Med Genet. Pubmed
Rots et al. (2024) Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes Am J Hum Genet. Pubmed
Rots et al. (2024) Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome Am J Hum Genet. Pubmed
Rots et al. (2024) Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global DNA methylation profile Clin Genet. Pubmed
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Bouman et al. (2024) Growth, body composition, and endocrine-metabolic profiles of individuals with Kleefstra syndrome provide directions for clinical management and translational studies Am J Med Genet A. Pubmed
Rots et al. (2023) The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder Am J Hum Genet. Pubmed
Wang et al. (2022) Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through the cAMP/PKA pathway Cell Rep. Pubmed
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Wang et al. (2021) SETD1A Mediated H3K4 Methylation and Its Role in Neurodevelopmental and Neuropsychiatric Disorders Front Mol Neurosci. Pubmed
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Iacono et al. (2018) Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome Nucleic Acids Res. Pubmed
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Kleefstra et al. (2009) Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype J Med Genet. Pubmed
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Kleefstra et al. (2006) Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome Am J Hum Genet. Pubmed
Kleefstra et al. (2005) Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome J Med Genet. Pubmed
Do you have questions about research at ENCORE? Or do you want to participate? Please contact us via encore@erasmusmc.nl or afspraak.genetica@erasmusmc.nl