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Review Article | Open Access

Twists and turns of the genetic story of mevalonate kinase-associated diseases: A review

IRMB, Univ Montpellier, INSERM, Montpellier 34090, France
Department of Medical Genetics, Rare Diseases and Personalized Medicine, Rare and Autoinflammatory Diseases Unit, CeRéMAIA, CHU, Montpellier 34000, France
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Abstract

Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions, all resulting from pathogenic variants in the mevalonate kinase gene (MVK). Their clinical manifestations are highly variable, ranging from more or less serious systemic disorders, such as hereditary recurrent fevers, to purely localized pathologies such as porokeratosis. The oldest condition identified as linked to this gene is a metabolic disease called mevalonic aciduria, and the most recent is disseminated superficial actinic porokeratosis, a disease limited to the skin. The modes of inheritance of MK-associated diseases also diverge among the different subtypes: recessive for the systemic subtypes and dominant with a post-zygotic somatic genetic alteration for MVK-associated porokeratosis. This review quickly retraces the historical steps that led to the description of the various MK-associated disease phenotypes and to a better understanding of their pathophysiology, then summarizes and compares the different genetic mechanisms involved in this group of disorders, and finally discusses the diverse causes that could underlie this phenotypic heterogeneity.

Keywords

Autoinflammatory diseaseGenetic diseaseMevalonate kinase deficiencyPorokeratosisSubtypes

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Genes & Diseases
Volume 9 Issue 4,
July 2022
Pages 1000-1007
DOI: 10.1016/j.gendis.2021.05.002
Cite this article:
Touitou I. Twists and turns of the genetic story of mevalonate kinase-associated diseases: A review. Genes & Diseases, 2022, 9(4): 1000-1007. https://doi.org/10.1016/j.gendis.2021.05.002

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Received: 20 January 2021
Revised: 19 April 2021
Accepted: 12 May 2021
Published: 09 June 2021
© 2021, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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