“…We show here that mice bearing combinations of hypomorphic and amorphic mutations in Mvk recapitulate the characteristic biochemical features of HIDS, the milder form of MKD. Like humans heterozygous for pathogenic MVK variants, who have reduced MK activity (Faraci et al, 2021; Houten et al, 1999; Neven et al, 2007) but lack any detectable defect in protein prenylation (Munoz et al, 2017; Munoz et al, 2019), heterozygous Mvk mutant mice showed normal prenylation of small GTPases despite a 25-50% decrease in MK activity. Homozygous Mvk VI/VI mice, harbouring the most frequent, hypomorphic HIDS missense mutation p.V377I (Boursier et al, 2021; Govindaraj et al, 2020; Houten et al, 2000; Ter Haar et al, 2016), had a mild prenylation phenotype that closely resembled the defect in PBMCs from a HIDS patient of the same genotype ( MVK V377I/V377I ) (Munoz et al, 2017; Munoz et al, 2019).…”