​Research in cancer genetics focus on a broad spectrum of inherited cancer conditions, including hereditary colorectal cancer and Lynch syndrome, melanoma, childhood cancers, breast cancer, gynecological cancers, hereditary breast–ovarian cancer, and hematological malignancies, as well as telomere biology disorders.

In addition, we conduct research on rarer cancer syndromes like endocrinological tumor syndromes and polyposis syndromes.

We also study somatic mutations and cytogenetic abnormalities, and their diagnostic, prognostic, and therapeutic implications in hematological malignancies.

Moreover, we examine the functional effect of variants of uncertain significance using RNA, protein and global assays.

Our research includes investigations of genetics, natural history, morbidity, and mortality to im-prove risk assessment, surveillance, and clinical management.

Researchers
Anna Byrjalsen, MD, PhD
Anne Marie Jelsig MD, PhD, Associate professor
Karin Wadt MD, PhD, Professor
Malene Djursby MD, PhD
Mette Klarskov Andersen MD, Dr. Med
Thomas Van Overeem Hansen MSc, PhD, Professor

​Research in the field of cardiovascular genetics seeks to understand how inherited genetic variations contribute to disorders of the heart and blood vessels, improving early diagnosis, risk prediction, and targeted management of individuals and families affected by these conditions.

Our research group focuses on improving the understanding and clinical management of heritable aortopathies and connective tissue–related cardiovascular disorders, including conditions such as Marfan syndrome, Loeys Dietz syndrome, vascular Ehlers Danlos syn-drome and other rare conditions. This work strengthens diagnostic accuracy through molecular characterization of genetic variants, whole genome sequencing, CNV analysis, RNA analysis, long-read sequencing and improved approaches to genetic counseling and variant interpretation

Additionally, secondary cardiovascular findings identified through broad genomic screening, while relatively rare, can carry important implications for clinical actionability, prompt cascade testing within families, and necessitate long term follow up to ensure appropriate management across generations. As genomic screening becomes more widely implement-ed, further research is essential to better understand the clinical significance of these findings, optimize follow up strategies, and refine guidelines for their integration into cardio-vascular care.

Researchers
Birgitte Rode Diness MD, PhD
Julius Hannibal Svensmark
Nicolai Kohring Tvergaard
Sofus Krüger Sølyst
Sophia Hammer-Hansen MD, PhD​​

​Imprinting disorders (ImpDis) are a group of congenital conditions caused by disturbed parent-of-origin–specific (imprinted) gene regulation, most often through abnormal DNA methylation at differentially methylated regions (DMRs). Clinically, they frequently present with growth abnormalities (overgrowth or growth restriction), variable neurodevelopmental involvement, and sometimes endocrine/metabolic features, with considerable phenotypic overlap between syndromes. Currently, there are 12 recognized imprinting disorders (syndromic entities), involving at least 13 disease-associated imprinted loci/regions.

At the molecular level, ImpDis can arise from (i) uniparental disomy (UPD), (ii) copy-number or structural variants affecting imprinted regions, (iii) primary epimutations (methylation errors), or (iv) sequence variants in imprinted genes or imprinting regulators; some individuals show multilocus imprinting disturbance (MLID), which has specific diagnostic and counselling implications.​

In our group we are mainly working on understanding the underlying molecular factors of imprinting disorders, mainly Beckwith-Wiedemann syndrome, Silver-Russell syndrome and multilocus imprinting disorbances (MLID), and we have published around 30 scientific publications linked to imprinting disorders,

Researchers
Zeynep Tümer MD, PhD, DMSc, Professor

Our key publications
Tümer et al. 2025. Maternal Effect Gene-Related Multilocus Imprinting Disturbances. Gene-Reviews, PMID: 40373180

Eggermann et al. 2023 Imprinting disorders. Nat Rev Dis Primers, PMID: 37386011

Brioude et al. 2018. Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol PMID: 29377879

Tümer et al. 2018. Structural and sequence variants in patients with Silver-Russell syndrome or similar features-Curation of a disease database. Hum Mutat, PMID: 29250858

Wakeling et al. 2014. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol, PMID: 27585961

​Inborn errors of metabolism (IEM) are inherited diseases caused by disturbances in key steps in human metabolic pathways, such as enzyme deficiencies, defective transporters, defective subcellular targeting etc. Enzyme deficiencies are most common and also the most common monogenic disorders. IEM are managed in Centre for Inherited Metabolic Diseases (CIMD). We are dedicated to advancing the understanding of metabolic diseases from diagnosis via newborn screening to treatment and follow-up The centre has national coverage for both children and adults and all main IEM are represented, such as amino acidopathies, incl. PKU, organic acidurias, fat oxidation disorders, lysosomal storage diseases and neurometabolic diseases.

From a research point of view, we aim to optimize and develop new biochemical as well as molecular-genetic diagnostics and monitoring tools, improve neonatal screening, improve national and European registration of patients and develop guidelines for diagnosis and management. Finally, we aim to develop new therapies for IEM, both as part of EU projects and as clinical trials for new orphan medicinal products in our clinical trial unit for rare dis-eases. This effort centers around nutritional therapy, enzyme replacement therapy, new vitamin substitutes and gene therapy. CIMD is a fully accredited member of the European Reference Network for Hereditary Metabolic Disorders.

Researchers
Elsebet Østergaard MD, PhD
Morten Dunø

​Mitochondrial disorders are the only group of diseases where two genomes, the nuclear and mitochondrial genomes, are involved. The disorders may affect both children and adults and lead to a wide range of symptoms.

Our research focuses on delineation of clinical phenotypes, genotype-phenotype correlations and identification of novel disease genes in mitochondrial disorders. We combine genome-wide sequencing approaches with RNA-seq, targeted mtDNA sequencing, computational tools and functional analyses to clarify the pathogenicity of novel variants and to improve diagnostic interpretation. Through this work we aim to increase diagnostic yield, better understand disease mechanisms, and support improved clinical management of affected individuals. Examples of diseases we are currently working on are: POLG-associated disease, TARS2-related disease, PDHA1-related dis-ease, COQ4-related disease.

Researchers
Elsebet Østergaard MD, PhD
Morten Dunø

​Neurodevelopmental disorders (NDDs) comprise a heterogeneous group of conditions caused by disturbances in brain development and function, typically presenting in early childhood. Clinically, they include developmental delay and intellectual disability, often accompanied by autism spectrum disorder, epilepsy, movement abnormalities, behavioral difficulties, or other neurological features. Many NDDs are caused by rare variants in single genes essential for brain development and function, most often arising de novo or inherited and altering gene function through loss- or gain-of-function mechanisms affecting proteins involved in neuronal signaling, chromatin regulation, synaptic organization, or ion-channel activity. Despite major advances in genome sequencing, many patients still remain without a clear molecular diagnosis.

Our research focuses on identifying and characterizing the genetic causes of rare monogenic NDDs. We combine genome-wide sequencing approaches with computational tools and functional analyses to clarify the pathogenicity of novel variants and to improve diagnostic interpretation. Through this work we aim to increase diagnostic yield, better understand disease mechanisms, and support improved clinical management of affected individuals. Examples of diseases we are currently working on are: DLG4-related synaptopathy, NDDs caused by variants in PGAP1 and UPF1 and fragile X syndrome.

Researchers:
Zeynep Tümer MD, PhD, DMSc, Professor
Elsebet Østergaard MD, PhD

Representative Publications
Hildonen et al. 2025. Biallelic loss-of function variants in ZNF142 are associated with a robust DNA methylation signature affecting a limited number of genomic loci. Eur J Hum Genet 33:896-903. PMID: 40410387

Furia et al 2024. The phenotypic and genotypic spectrum of individuals with mono- or biallelic ANK3 variants. Clin Genet 106:574-584. PMID: 38988293

Kassabian et al. 2024. Developmental epileptic encephalopathy in DLG4-related synaptopathy. Epilepsia 65:1029-1045. PMID: 38135915

Tümer et al. 2023. DLG4-related synaptopathy. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023

Oppermann et al. 2023. CUX1-related NDD: Deep insights into phenotype-genotype spectrum and pathology. Eur J Hum Genet 31:1251-1260. PMID: 37644171

​There are over 600 distinct genetic neuromuscular diseases (NMD), caused by variants in more than 650 different genes. These conditions, which include various muscular dystrophies, myopathies, and neuropathies, are individually rare but collectively affect about 1 in 1,000 individuals worldwide. They are characterized by progressive muscle degeneration and weakness due to genetic variants which primarily or secondarily impair skeletal muscle function. Most of the conditions display autosomal recessive, autosomal dominant or X-linked inheritance; the onset can occur in childhood and have a severe progression or later in life with a slower course.

Our research focuses on identifying and characterizing the genetic causes of NMD. We combine genome-wide and RNA sequencing approaches with computational tools and functional analyses to identify novel disease genes, clarify the pathogenicity of novel variants and to improve diagnostic interpretation. Through this work we aim to increase diagnostic yield, better understand disease mechanisms, and support improved clinical management of affected individuals. Examples of dis-eases we are currently working on include Duchenne muscular dystrophy, MYL1-related myopathy and COL6A1-related muscular dystrophy.

Genetic neurodegenerative disorders
Neurodegenerative disorders are a clinically, pathologically and genetically diverse group of disorders characterized by progressive degeneration of neurons. Examples of neurodegenerative dis-eases are Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and prion diseases. Some neurogenerative diseases occur sporadic but can also be caused by specific genetic variants including repeat expansions.

Our clinical work as well as research aims to identify and further characterize the genetic background for rare genetic neurodegenerative disorders. Advances in genetic testing methods in-crease diagnostic yield and thereby improve genetic counseling and risk information to family members and can potentially determine eligibility for clinical trials. We combine genome-wide sequencing approaches and targeted analyses for repeat expansion disorders with functional analyses to improve diagnostic yield and determine the pathogenicity of novel variants and to improve diagnostic interpretation. We participate in research focusing on delineating the clinical phenotype and genotype-phenotype correlations in close collaboration with translational research environments to ensure that new knowledge is effectively integrated into patient care.

Researchers
Elsebet Østergaard MD, PhD
Lisbeth Birk Møller Senior Scientist
Morten Dunø
Suzanne Lindquist MD, PhD
Trine Bjørg Hammer MD, PhD
Zeynep Tümer MD, PhD, DMSc, Professor​​

Genetic eye disorders are the leading cause of blindness and severe visual impairment in children and young adults. These conditions may present as isolated ocular disorders or as part of broader syndromic disease, reflecting their marked genetic and clinical complexity. Genetic eye disorders can affect all parts of the eye, including the retina, optic nerve, lens, iris, and cornea, with more than 500 genes known to be involved, and new disease genes that continue to be identified.

We investigate the molecular basis of inherited eye disorders such as retinal dystrophies, albinism, optic atrophy, congenital malformations, and early-onset glaucoma. Our aim is to identify disease-causing variants and understand how genetic alterations disrupt ocular development and function. This knowledge supports precise diagnostics, improved genetic counselling, and the development of more personalized approaches to treatment and prevention of visual impairment. A key focus of our research is detailed genotype–phenotype correlation studies in affected families. By combining comprehensive genomic analyses, with thorough clinical characterization, we seek to uncover novel disease mechanisms and to better understand reduced penetrance and variable expressivity. To functionally characterize identified variants, we develop advanced experimental models including induced pluripotent stem cell–derived retinal pigment epithelium and CRISPR-based activation systems. In addition, we investigate selected genetic findings in zebrafish models to assess their functional impact in vivo, enabling translation of genetic discoveries into biological insight and future therapeutic strategies.

Researchers
Mette Bertelsen Vardrup
Karen Grønskov
Lisbeth Birk Møller​

​Hearing impairment is the most common congenital sensory impairment worldwide. More than half of all congenital and early onset cases have a genetic cause, and over 150 genes are currently known to underlie non-syndromic hearing impairment. In addition, hundreds of clinically distinct syndromic forms have been described with more than 500 genes identified. Despite major advances in sequencing technologies, many patients and families still lack a precise molecular diagnosis after routine diagnostic testing.

Our research focuses on uncovering new disease mechanisms and identifying novel disease genes underlying both non-syndromic and syndromic hearing impairment. A central component of our work is detailed genotype–phenotype correlation studies, where we integrate comprehensive genomic analyses with careful clinical characterization to better understand phenotypic variability and disease progression. We aim to resolve unsolved families by applying advanced sequencing strategies, including long-read sequencing, which enables detection of structural variants, complex genomic regions, and variants that are not captured by conventional approaches and multi-omics approaches, for example transcriptomics and 3D-genome organization studies. Furthermore, we are integrating artificial intelligence and functional studies for resolving variants of uncertain significance (VUS).  Additionally, we are conducting a focused project on the comprehensive characterization of complex genomic regions such as STRC, a gene complicated by the presence of a highly homologous pseudogene, where long-read technologies significantly improve analytical accuracy.

Our research has strong clinical relevance. Newly identified genes and mechanisms are continuously improving molecular diagnostic yield, enabling more precise prognostic assessment and genetic counselling. Ultimately, understanding the biological basis of hearing impairment provides the foundation for optimizing treatment and future therapeutic strategies.

Researchers
Mette Bertelsen Vardrup MD
Nanna Dahl Rendtorff
Lisbeth Tranebjærg MD

​At the Department of Clinical Genetics, we have extensive experience in the characterization of structural genomic variation. We apply both state-of-the-art technologies, such as short- and long-read sequencing, to resolve rearrangements at high resolution, and classical cytogenetic approaches, including karyotyping and fluorescence in situ hybridization (FISH), to visualize genomic organization at the single-cell level. This integrative approach enables a detailed characterization of even highly complex structural rearrangements, such as chromothripsis and chromosynthesis, and correlate these findings with the clinical phenotype.

We have a well-established collaboration with our colleagues in the other Clinical Genetic Departments in Denmark, the Department of Cellular and Molecular Medicine, University of Copenhagen and Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden

Researchers
Lusine Nazaryan-Petersen
Marie Balslev-Harder
Mads Bak
Iben Bache MD

​At the Department of Clinical Genetics, we have extensive experience in genome-wide DNA methylation (DNAm) profiling and DNAm signature analysis. We apply state-of-the-art long-read sequencing technologies, including Nanopore- and PacBio-based methylation profiling, to detect and characterize disease-associated DNAm signatures. By integrating methylation data with clinical and genomic findings, we are able to support the interpretation of genetic variants and improve the diagnosis of rare genetic disorders. This approach enables the identification of distinct epigenetic patterns associated with specific molecular mechanisms and clinical phenotypes.

Researchers
Mathis Hildonen
Zeynep Tümer MD, PhD, DMSc, Professor

Our key publications
Hildonen, M., Ciolfi, A., Ferilli, M., Cappelletti, C., Al Alam, C., Amor. David, Barakat, T. S., Benoit, V., Birk, O., Callewaert, B., Cazurro-Gutierrez, A., De Wachter, M., Doco-Fenzy, M., Gómez-Puertas, P., Hammer, T., Jamra, R. A., Kaiyrzhanov, R., Kamemaya, S., Keren, B., … Tümer, Z., Tartaglia, M. (2025). Biallelic loss-of-function variants in ZNF142 are associated with a robust DNA methylation signature affecting a limited number of genomic loci. European Journal of Human Genetics.

Hildonen, M., Ferilli, M., Hjortshøj, T. D., Dunø, M., Risom, L., Bak, M., Ek, J., Møller, R. S., Ciolfi, A., Tartaglia, M., & Tümer, Z. (2023). DNA methylation signature classification of rare disorders us-ing publicly available methylation data. Clinical Genetics, 103(6), 688–692. https://doi.org/10.1111/cge.14304

Hildonen, M., Ferilli, M., Krey, I., Kohnen, O., Cappelletti, C., Platzer, K., Ciolfi, A., Jamra, R. A., Tartaglia, M., & Tümer, Z. (2025). Diagnosis of Angelman Syndrome, With 66 Years of Delay, Using Hypothesis-Free DNA Methylation Profiling. Clinical Genetics, 108(3), 369–370. https://doi.org/10.1111/cge.70000

Hildonen, M., Mariani, L., Dalsberg, J., Bak, M., Weksberg, R., Choufani, S., & Tümer, Z. (2026). Clinical Feasibility of Long-Read WGS for DNA Methylation Signature Analysis. Clinical Genetics, 109(4), 725–729. https://doi.org/10.1111/cge.70108

​Research in functional analysis focuses on elucidating the biological impact of genetic variants, particularly variants of uncertain significance (VUS), to improve their clinical interpretation.

We perform RNA-based analyses to investigate the effects of genetic variants on splicing and gene expression.

In addition, we develop and apply CRISPR/Cas-based functional assays to characterize the consequences of VUS in relevant cellular models.

By integrating RNA studies with genome editing technologies, we aim to establish robust functional evidence for variant classification.

Our research contributes to a better understanding of disease mechanisms and supports more accurate genetic diagnostics and clinical decision-making.

Researchers
Jane Hübertz Frederiksen
Thomas Van Overeem Hansen MSc, PhD, Professor​​