Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome

  title={Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome},
  author={Joost P. H. Drenth and Laurence Cuisset and Gilles Grateau and Christian Vasseur and Saskia D. Velde-Visser and J.G.N. de Jong and Jacques S. Beckmann and Jos W. M. van der Meer and Marc Delpech contributing members of the International Group},
  journal={Nature Genetics},
Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS; MIM 260920) is a rare, apparently monogenic, autosomal recessive disorder characterized by recurrent episodes of fever accompanied with lymphadenopathy, abdominal distress, joint involvement and skin lesions. All patients have high serum IgD values (>100 U/ml) and HIDS 'attacks' are associated with an intense acute phase reaction whose exact pathophysiology remains obscure. Two other hereditary febrile disorders have been described… 

Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome

It is proposed that the diagnostic screen of MVK in HIDS should be first directed on V377I and I268T mutations, which 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.

Novel mutations of MVK gene in Japanese family members affected with hyperimmunoglobulinemia D and periodic fever syndrome

A family of eldest son and monozygotic twin younger sisters with characteristic syndrome of HIDS, but normal level of IgD, is described, the first case in which exon skipping mutation of the MVK gene has been certainly identified at the genomic DNA level.

[MVK gene abnormality and new approach to treatment of hyper IgD syndrome and periodic fever syndrome].

  • T. Naruto
  • Medicine, Biology
    Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology
  • 2007
During febrile episodes, urinary mevalonate concentrations were found to be significantly elevated in patients, and the therapy attempt with statins, which is inhibited the next enzyme after HMG-CoA reductase, or inhibit the proinflammatory cytokines.

Periodic Fever in MVK Deficiency: A Patient Initially Diagnosed With Incomplete Kawasaki Disease

This case shows that the initial presentation of MKD can be indistinguishable from incomplete Kawasaki syndrome, and when fever recurs in Kawasaki Syndrome, other (auto-)inflammatory diseases must be ruled out to avoid inappropriate diagnostic procedures, ineffective interventions, and treatment delay.

Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome

A gene, called CIAS1, is expressed in peripheral blood leukocytes and encodes a protein with a pyrin domain, a nucleotide-binding site (NBS, NACHT subfamily) domain and a leucine-rich repeat (LRR) motif region, suggesting a role in the regulation of inflammation and apoptosis.

Spectrum of clinical features and genetic variants in mevalonate kinase (MVK) gene of South Indian families suffering from Hyperimmunoglobulin D Syndrome

A case series of HIDS from India, which includes ten patients from six families who presented with a wide spectrum of clinical features such as recurrent fever, oral ulcers, rash, arthritis, recurrent diarrhea, hepatosplenomegaly, and high immunoglobulin levels is reported.

MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever

It is demonstrated that MKD is a common cause of recurrent fever also in the Italian population, where it is associated with both a wide spectrum of previously unreported MVK mutations and peculiar phenotypic features.

Hyper-IgD syndrome and hereditary periodic fever syndromes

The hyper-IgD syndrome (HIDS) is a rare autosomal recessive inflammatory disorder characterized by recurrent fever, increased serum IgD and generalized inflammation that persists during the entire life although frequency and severity tend to diminish with age.

A Novel Missense Mutation in MVK Associated With MK Deficiency and Dyserythropoietic Anemia

A patient with MKD and congenital dyserythropoietic anemia was diagnosed with mild dysmorphic features and elevated urinary mevalonic acid levels in the absence of an inflammatory attack, suggesting an intermediate phenotype between HIDS and MA.

Identification of a novel mevalonate kinase gene mutation in combination with the common MVK V377I substitution and the low-penetrance TNFRSF1A R92Q mutation

A girl with heterozygosity for the common MVK V377I mutation and for a novel T1132 → C transition, leading to the exchange of serine by proline at amino-acid position 378 presented only with mild clinical features typical of HIDS and slightly increased immunoglobulin D levels, but a distinctly diminished MK activity.



Linkage of familial Hibernian fever to chromosome 12p13.

Cumulative multipoint linkage analyses indicate that an FHF gene is likely to be located in an 8-cM interval between D 12S77 and D12S356, with a maximum LOD score of 3.79, and it is proposed that these markers should be tested in other families that have autosomal dominant periodic fever, as a prelude to identification of the FHF-susceptibility gene.

Gene localization for an autosomal dominant familial periodic fever to 12p13.

Gen localization in a family with a benign autosomal dominant familial periodic fever (FPF) syndrome characterized by recurrent fever associated with abdominal pain is reported, the first of the periodic-fever genes, other than FMF, to be mapped.

A candidate gene for familial Mediterranean fever

A minimal co-segregating region of 60 kb containing the FMF gene (MEFV) is defined and one of these transcripts encodes a new protein (marenostrin) related to the ret-finger protein and to butyrophilin.

Mucopolysaccharidosis type I: Identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations

Haplotype analysis using polymorphisms linked to the IDUA locus demonstrated that each mutation occurs on a different specific haplotype, suggesting that individuals with each of these common mutations derive from common founders.

Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome.

Findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.

Clinical and biochemical phenotype in 11 patients with mevalonic aciduria.

It is concluded that although patients with mevalonic aciduria have a recognizable phenotype of serious clinical manifestations, some patients are likely to remain undiagnosed and may be found in a variety of subspecialty clinics, including neurology, gastroenterology, cardiology, and genetics.

Hyperimmunoglobulinemia D and Periodic Fever Syndrome: The Clinical Spectrum in a Series of 50 Patients

The hyper-IgD syndrome is distinct from other periodic fever syndromes like systemic-onset juvenile rheumatoid arthritis, adult-onsets Still disease, and familial Mediterranean fever and treatment is supportive.

Clinical spectrum of familial Hibernian fever: a 14-year follow-up study of the index case and extended family.

The characteristic clinical features and natural history of FHF distinguish it from other periodic fever syndromes and the discovery of amyloidosis related to FHF alters the prognosis associated with this condition and emphasizes the need for effective treatment strategies.