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Clinical and Experimental Dermatology Apr 2024
PubMed: 38680042
DOI: 10.1093/ced/llae156 -
International Journal of Dermatology Jun 2024
PubMed: 38853388
DOI: 10.1111/ijd.17268 -
Clinical Genetics Mar 2024The evolutionarily conserved mevalonate pathway plays an important role in the synthesis of cholesterol and isoprenoid compounds. Mevalonate kinase (MVK) and...
The evolutionarily conserved mevalonate pathway plays an important role in the synthesis of cholesterol and isoprenoid compounds. Mevalonate kinase (MVK) and phosphomevalonate kinase (PMVK) enzymes regulate key rate-limiting steps in this pathway by sequentially phosphorylating mevalonic acid to yield downstream metabolites that regulate protein prenylation and cell signaling. Biallelic pathogenic variants in MVK cause a spectrum of rare autoinflammatory disorders that encompass milder forms of hyper-IgD syndrome (HIDS) at one end and the more severe mevalonic aciduria on the other. In contrast, pathogenic variants reported in PMVK are heterozygous and associated with porokeratosis, a skin disorder with no systemic manifestations. Recently, biallelic variants in PMVK were reported as a cause for an autoinflammatory disorder for the first time in two unrelated patients. In this study, we describe a child with recurrent arthritis and a HIDS-like phenotype harboring a novel homozygous variant c.398 C>T (p.Ala133Val) in PMVK. Mononuclear cells isolated from the patient showed significantly elevated production of interleukin 1β, a key cytokine that shapes the inflammatory response in HIDS. Protein modeling studies suggested potential defects in PMVK enzyme activity. These results posit a further expanding of the genotypic spectrum of autoinflammatory disease to include biallelic PMVK variants.
Topics: Child; Humans; Genotype; Mevalonate Kinase Deficiency; Phenotype; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases (Phosphate Group Acceptor)
PubMed: 38018277
DOI: 10.1111/cge.14451 -
The Australasian Journal of Dermatology Jun 2024
Topics: Humans; Porokeratosis; Dermoscopy; Ultraviolet Rays; Male; Fluorescence; Female
PubMed: 38421822
DOI: 10.1111/ajd.14241 -
The American Journal of Dermatopathology Jun 2024
PubMed: 38842349
DOI: 10.1097/DAD.0000000000002641