Work

A mild skeletal phenotype with overlapping features of Miller syndrome and functional characterisation of two new variants of human dihydroorotate dehydrogenase

Year: 2024

Type: article

Abstract: variant R135C, we aimed to study the effect on enzyme activity of the two variants D277N and P43L to determine pathogenicity and possibly a genotype-phenotype relationship on the R135C background. We found a significant reduction in enzyme activity for both variants. The variant P43L showed a more pronounced loss of function in all assays compatible with other pathogenic variants reported in Miller, whereas the D277N variant showed milder changes that could reflect the mild phenotypic features in our patient. Yet due to a lack of a known threshold of residual enzyme activity to determine pathogenicity, this needs to be confirmed in further studies.

Source: Heliyon

DOI: 10.1016/j.heliyon.2024.e38659