Hyperimmunoglobulinaemia D and Periodic Fever: A New Syndrome

Meer, JosW.M. Van Der; Rádl, J.; Meyer, ChrisJ.L.M.; Vossen, J. M.; Nieuwkoop, JannyA. Van; Lobatto, S.; Furth, R. van

doi:10.1016/s0140-6736(84)92505-4

Cited by 299 publications

(129 citation statements)

References 20 publications

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“…Reasoning from the clinical phenotype, we chose to investigate apoptosis of lymphocytes in HIDS. Lymphadenopathy, lymphocytic infiltrates in skin biopsies, and many B lymphocytes containing IgD in the cytoplasm in bone marrow can be observed in HIDS, 11,12 and this may be related to the lymphocyte apoptosis defect. In the other periodic fever syndromes, different cell types are more prominent and point to cell-specific defects.…”

Section: Resultsmentioning

confidence: 99%

Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome

Bodar

Hilst

Heerde³

et al. 2006

Blood

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Hereditary periodic fever syndromes are characterized by incapacitating attacks of fever and generalized inflammation. While the mutated genes for the major syndromes in this group are known, the pathogenesis remains unclear. The aim of this study was to investigate apoptosis in patients with periodic fever as a possible pathogenic factor. We measured anisomycin-induced apoptosis with annexin-V flow cytometry and caspase-3/7 activity in peripheral-blood lymphocytes from symptom-free patients with hyper-IgD and periodic fever syndrome (HIDS; n ‫؍‬ 10), TNF-receptor-associated periodic syndrome (TRAPS; n ‫؍‬ 7), and familial Mediterranean fever (FMF; n ‫؍‬ 2). HIDS lymphocytes showed a decreased percentage of apoptosis during remission by both methods compared with controls (17.8% vs 55.4%), whereas no difference was observed in TRAPS or FMF lymphocytes. This defective apoptosis of lymphocytes may be a central pathogenic mechanism in HIDS, since dysfunction of one of the inhibitory mechanisms to curtail the immunologic response could cause an unbridled generalized inflammation after a trivial stimulus.

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Section: Resultsmentioning

confidence: 99%

Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome

Bodar

Hilst

Heerde³

et al. 2006

Blood

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“…These results suggest that MK deficiency would be among the most common recessive disorders in the Netherlands; however, this does not appear to be in line with the actual findings in the Dutch population. Since the first description of HIDS in 1984 23 only 74 Dutch patients have been diagnosed (sibs included). Of these, 47 have been confirmed to result from MK deficiency, which is denoted as classic-type HIDS.…”

Section: Resultsmentioning

confidence: 99%

Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands

et al. 2003

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Hyper-IgD and periodic fever syndrome (HIDS) and mevalonic aciduria (MA) are two autosomal recessive disorders that both are caused by a deficient activity of the enzyme mevalonate kinase (MK) due to mutations in the encoding gene (MVK). The most frequently occurring MVK mutation, V377I (1129G4A), has been identified exclusively in HIDS patients. Other common mutations have been associated with both HIDS and MA. To estimate the incidence of MK deficiency in the Netherlands, we determined the carrier frequency of the V377I mutation in genomic DNA extracted from anonymised newborn screening cards by PCR-RFLP. We found 14 carriers among 2138 analysed samples (1 : 153). Based on the V377I allele frequency of 42% in patients diagnosed with MK deficiency, the carrier frequency of any MVK mutation in the Dutch population can be calculated as 1 : 65. This predicts a disease incidence between 1 in 5196 and 1 in 53 656, which is far more than actually observed. Although under-diagnosis of patients with MK deficiency remains possible, this discrepancy probably is due to a reduced penetrance of V377I homozygosity. Analysis of the distribution of the V377I allele within patients carrying MVK mutations revealed that this was not according to the Hardy -Weinberg equilibrium principle, most probably due to an under-representation of V377I homozygotes in HIDS. Homozygotes for V377I might exhibit a much milder phenotype of MK deficiency or no disease-phenotype at all.

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“…We consider patient 1 as typical HIDS because she possessed the most frequent MVK mutation (V377I) and displayed the classical features of HIDS, being the first HIDS patient diagnosed. 16 This further study allows us to draw a more complete picture of the biochemical and mutational differences between HIDS and mevalonic aciduria. In our HIDS cohort the MK enzyme activities vary widely and, as we previously observed, 4 the lower values may overlap with those observed in mevalonic aciduria.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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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. European Journal of Human Genetics (2001) 9, 260 ± 266.

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Hyperimmunoglobulinaemia D and Periodic Fever: A New Syndrome

Cited by 299 publications

References 20 publications

Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome

Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome

Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands

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

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