Irena Muffels

University Medical Center Utrecht | UMC Utrecht · Wilhelmina Children´s Hospital

Posterpresentation at the SSIEM Conference 2024 in Porto

Mono‐allelic DHDDS variants are associated with seizures, intellectual disability, and movement disorders. The age of onset and progression rates of symptoms vary greatly among patients, spanning from infancy to late adulthood. Yet, the reasons behind this clinical variability and the underlying pathophysiological mechanisms of the disease have rem...

Inborn-Errors of Metabolism (IEM) are genetic disorders resulting from mutations in genes encoding proteins involved in biochemical-metabolic pathways. However, some IEMs lack specific biochemical markers. Early incorporation of next-generation-sequencing (NGS) including whole exome sequencing (WES) into the diagnostic algorithm of IEMs herein prov...

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular co...

The recent identification of NAA80/NAT6 as the enzyme that acetylates actins generated new insight in the process of post-translational actin modifications, however, the role of NAA80 in human physiology and pathology has not been clarified yet. We report two individuals from a single family harboring a homozygous c.389T>C, p.(Leu130Pro) NAA80 gene...

Located in the critical 1p36 microdeletion region, the chromodomain helicase DNA-binding protein 5 ( CHD5 ) gene encodes a subunit of the nucleosome remodeling and deacetylation (NuRD) complex required for neuronal development. Pathogenic variants in six of nine chromodomain (CHD) genes cause autosomal dominant neurodevelopmental disorders, while C...