Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome.
Publication year
2001Source
European Journal of Human Genetics, 9, 4, (2001), pp. 260--6ISSN
Publication type
Article / Letter to editor

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Organization
Gastroenterology
Internal Medicine
Journal title
European Journal of Human Genetics
Volume
vol. 9
Issue
iss. 4
Page start
p. 260-
Page end
p. 6
Subject
The role of cytokines in the pathophysiology of febrile illnesses and in host defense against infections; Metabolic aspects of gastrointestinal diseases; De rol van cytokinen in de pathofysiologie van koortsende ziekten en in de afweer tegen infecties; Metabole aspecten van maag-, darm- en leveraandoeningenAbstract
Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is an autosomal recessive inflammatory disorder characterised by recurrent episode of fever associated with lymphadenopathy, abdominal distress, joint involvement and skin lesions. We recently demonstrated that mutations in the mevalonate kinase gene (MVK) are associated with HIDS. Direct DNA sequencing was done to screen the entire coding region of MVK in 25 unrelated patients with HIDS. Mutations were detected in the coding region of the gene including 11 missense mutations, one deletion, the absence of expression of one allele, as well as three novel polymorphisms. Seven of these mutations are novel. The large majority of the patients were compound heterozygotes for two mutations. Of these, V377I (G-->A) is the most common mutation occurring in 20 unrelated patients and was found to be associated with I268T in six patients. Mutations were associated with a decrease of mevalonate kinase (MK) (ATP:mevalonate 5-phosphotransferase, EC 2.7.I.36) enzymatic activity but not as profound as in mevalonic aciduria, a syndrome also caused by a deficient activity of MK. In HIDS the mutations are located all along the protein which is different from mevalonic aciduria where MK mutations are mainly clustered to a same region of the protein. On the basis of this study, we propose that the diagnostic screen of MVK in HIDS should be first directed on V377I and I268T mutations. Three patients are also described to illustrate the genotypic and phenotypic overlap with mevalonic aciduria.
This item appears in the following Collection(s)
- Academic publications [227881]
- Faculty of Medical Sciences [86219]
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