25 August 2021

Floor Baas, master and honours student Biomedical Sciences, and Dorine Swinkels, theme Renal disorders, have published an article in Clinical Chemistry about assessment of pathogenicity of genetic variants in hereditary hemochromatosis.

Background

Hereditary hemochromatosis (HH) is a genetic disease, leading to iron accumulation and possible organ damage. Patients are usually homozygous for p. Cys282Tyr in the homeostatic iron regulator gene but may have mutations in other genes involved in the regulation of iron. Next-generation sequencing is increasingly being utilized for the diagnosis of patients, leading to the discovery of novel genetic variants. The clinical significance of these variants is often unknown.

Content 

Determining the pathogenicity of such variants of unknown significance is important for diagnostics and genetic counseling. Predictions can be made using in silico computational tools and population data, but additional evidence is required for a conclusive pathogenicity classification. Genetic disease models, such as in vitro models using cellular overexpression, induced pluripotent stem cells or organoids, and in vivo models using mice or zebrafish all have their own challenges and opportunities when used to model HH and other iron disorders. Recent developments in gene-editing technologies are transforming the field of genetic disease modeling.

In summary, this review addresses methods and developments regarding the discovery and classification of genetic variants, from in silico tools to in vitro and in vivo models, and presents them in the context of HH. It also explores recent gene-editing developments and how they can be applied to the discussed models of genetic disease.

read more

Related news items


Sensitive blood-test as patient-friendly alternative for bone marrow-based cancer monitoring

20 October 2021

Hans Jacobs and Pieter Langerhorst, theme Cancer development and immune defense, and colleagues are one step closer to implementation of personalized diagnostics for bone marrow-based cancer monitoring.

read more

Register for peer coaching for RIMLS PhD candidates

20 October 2021

As a PhD candidate, you are in the lead of your own learning process. But you don’t need to do this alone: Register for the peer-coaching group ‘Stay in the lead – Together’ before 11 November 2021.

read more

Frans Russel appointed member Supervisory Committee of RIVM

20 October 2021

Frans Russel, theme Renal disorders, has been appointed by The Minister of Health, Welfare and Sport (VWS).

read more

Often additional demand for care without decreasing number of admissions Telemonitoring in chronic heart failure not unqualifiedly positive

19 October 2021

To contain rising healthcare costs, digitization of healthcare is often seen as a solution. Researchers at the Radboudumc examined the use of telemonitoring in chronic heart failure. Does this reduce hospital admissions and visits to the emergency room?

read more

RIMLS awards call for nominations

19 October 2021

RIMLS awards several prizes to stimulate and honor our (young) researchers. Please find here an overview of the upcoming awards. Deadline 24 November 2021.

read more

Epigenetics: Immunization is passed on to offspring Mice transmit adaptations to infections to next generations

19 October 2021

Does an infection affect the immunization of subsequent generations? It does, according to research now published in Nature Immunology.

read more