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J P Drenth

Publications and source records attributed to J P Drenth.

At least 19 recordsLinked to original sources
PubMed2001

The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32.

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. The symptoms are generally refractory to treatment and persist throughout life. Five kindreds with multiple cases of primary erythermalgia were identified, and the largest was subjected to a genomewide search. We detected strong evidence for linkage of the primary erythermalgia locus to markers from chromosome 2q. The highest LOD score (Z) was obtained with D2S2330 (Z(max) = 6.51). Analysis of recombination events identified D2S2370 and D2S1776 as flanking markers, on chromosome 2q31-32. This defines a critical interval of 7.94 cM that harbors the primary erythermalgia gene. Affected members within the additional families also shared a common haplotype on chromosome 2q31-32, supporting our linkage results. Identification of the primary erythermalgia gene will allow a better clinical classification of this pleomorphic group of disorders.

Child↗
PubMed2001

[From gene to disease; tumor necrosis factor receptor and a syndrome of familial periodic fever].

Familial Hibernian fever (FHF) is a rare hereditary syndrome that causes periodic attacks of fever and inflammation. It is an autosomal dominantly inherited disorder. The gene involved in FHF encodes for a receptor for tumour necrosis factor (TNFR1). These mutations are thought to result in impaired shedding of the receptor from the cell membrane, leading to deficient curtailing of the inflammatory reaction. The acronym TRAPS (TNF-receptor associated periodic syndrome) has been proposed as a more accurate name.

Alleles↗
PubMed2001

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

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.

Adult↗
PubMed2001

Hyper-immunoglobulin A in the hyperimmunoglobulinemia D syndrome.

The hyperimmunoglobulinemia D syndrome (HIDS) is an autosomal recessive disorder characterized by recurrent febrile attacks with abdominal, articular, and skin manifestations. Apart from elevated immunoglobulin D (IgD) levels (>100 IU/ml), there are high IgA levels in the majority of cases. Mutations in the gene encoding mevalonate kinase constitute the molecular defect in HIDS. The cause of elevated IgA concentrations in HIDS patients remains to be elucidated. We studied the hyper-IgA response in serum of a group of HIDS patients. Elevated IgA concentrations result from increased IgA1 concentrations. IgA and IgA1 concentrations correlated significantly with IgD concentrations, and levels of IgA polymers were significantly higher than the levels in healthy donors. These results indicate a continuous, presumably systemic, stimulation of IgA in HIDS patients.

Adolescent↗
PubMed2000

[From gene to disease; hereditary pancreatitis].

Hereditary pancreatitis is an autosomal dominant form of chronic pancreatitis. It presents with recurrent attacks of acute pancreatitis, usually starting in early childhood. The attacks may vary from mild abdominal pain to pancreatic necrosis, splenic vein thrombosis, pseudocysts and death. Ultimately chronic pancreatitis ensues with unrelenting pain, calcifications, endocrine and exocrine dysfunction. The penetrance is estimated at 80%. With the use of genetic linkage analysis the gene for hereditary pancreatitis was placed on the long arm of chromosome 7 (7q35). Mutational analysis identified cationic trypsinogen as the disease gene. Cationic trypsinogen mutations are thought to result in resistance of this molecule to autolysis.

Adult↗
PubMed2000

[Aortic stenosis and intestinal blood loss from angiodysplasia: valve replacement is a therapeutic option].

Three patients, men aged 67, 68 en 61, had for many years suffered from recurrent iron deficient anaemia and were found to have an aortic stenosis. Coloscopy identified angiodysplastic lesions, and we suspected additional lesions in the small intestine. Despite surgical and endoscopic treatment, gastrointestinal bleeding recurred. Replacement of the stenosed aortic valve with a bioprosthesis led to a recovery in the haemoglobin levels of all three patients. Angiodysplasias are a common source of gastrointestinal bleeding with an invisible origin. Data from the literature suggest an association between aortic stenosis and angiodysplasia although epidemiological evidence is lacking.

Aged↗
PubMed2000

[Identification of the gene for hyper-IgD syndrome: a model of modern genetics].

Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is a rare autosomal recessive disorder. Patients suffer from recurrent attacks (3-6 days) with fever, abdominal distress, lymphadenopathy, skin lesions and arthralgias. Patients display a constantly elevated serum IgD which serves as a biological marker of the disease. Recently, the gene for HIDS was discovered by two independent groups using positional and functional cloning methods. One group used linkage analysis (positional cloning) and was able to locate the gene for HIDS on the long arm of chromosome 12 (12q24). Mevalonate kinase was an interesting candidate gene because patients with a near complete absence of this enzyme (mevalonic aciduria) do exhibit attacks of fever. Indeed subsequent data showed that there was a decreased enzyme activity due to missense mutations in the mevalonate kinase gene. The other group detected slightly elevated urinary excretion of mevalonic acid during attacks in a HIDS patient (functional cloning). The enzyme activity of mevalonate kinase was lower in cultured cells and sequence analysis identified several missense mutations in cDNA encoding for mevalonate kinase. Mevalonate kinase is a key enzyme in the cholesterol synthesis pathway and it is rather surprising that a defect in the cholesterol metabolism can cause a periodic inflammatory disease such as HIDS.

Biomarkers↗
PubMed2000

Behçet's disease.

Explore the source record for details and available documents.

Behcet Syndrome↗
PubMed1999

Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group.

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. Familial Mediterranean fever (MIM 249100) is an autosomal recessive disorder affecting mostly populations from the Mediterranean basin and is caused by mutations in the gene MEFV (refs 5,6). Familial Hibernian fever (MIM 142680), also known as autosomal dominant familial recurrent fever, is caused by missense mutations in the gene encoding type I tumour necrosis factor receptor. Here we perform a genome-wide search to map the HIDS gene. Haplotype analysis placed the gene at 12q24 between D12S330 and D12S79. We identified the gene MVK, encoding mevalonate kinase (MK, ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36), as a candidate gene. We characterized 3 missense mutations, a 92-bp loss stemming from a deletion or from exon skipping, and the absence of expression of one allele. Functional analysis demonstrated diminished MK activity in fibroblasts from HIDS patients. Our data establish MVK as the gene responsible for HIDS.

Amino Acid Sequence↗
PubMed1999

Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44.

The Muckle-Wells syndrome (MWS) is a hereditary inflammatory disorder characterized by acute febrile inflammatory episodes comprising abdominal pain, arthritis, and urticaria. Progressive nerve deafness develops subsequently, and, after several years, the disease is complicated by multiorgan AA-type amyloidosis (i.e., amyloidosis derived from the inflammatory serum amyloid-associated protein) (MIM 191900) with renal involvement and end-stage renal failure. The mode of inheritance is autosomal dominant, but some sporadic cases have also been described. No specific laboratory findings have been reported. The genetic basis of MWS is unknown. Using a genomewide search strategy in three families, we identified the locus responsible for MWS, at chromosome 1q44. Our results indicate that the gene is located within a 13.9-cM region between markers D1S2811 and D1S2882, with a maximum two-point LOD score of 4. 66 (recombination fraction.00) at D1S2836 when full penetrance is assumed. Further identification of the specific gene that is responsible for MWS will therefore provide the first biological element for characterizing MWS, other than doing so on the basis of its variable clinical expression.

Abdominal Pain↗
PubMed1999

Hereditary fevers.

Hereditary fevers are a group of rare disorders of the inflammatory response. Clinical features include recurrent attacks of fever and organ-localized inflammation. Minimal clinical variations, a unique biochemical-specific abnormality, and the mode of genetic inheritance distinguish the three main diseases: familial Mediterranean fever, hyperimmunoglobulinemia D and periodic fever syndrome, and autosomal dominant recurrent fever. The complete elucidation of pathogenesis of these intriguing disorders will be provided by the genetic studies currently in progress.

Familial Mediterranean Fever↗
PubMed1999

Activation of the cytokine network in familial Mediterranean fever.

OBJECTIVE: To elucidate the role of cytokines in the pathogenesis of familial Mediterranean fever (FMF), an inherited disease characterized by attacks of serosal membrane inflammation. METHODS: Blood samples were obtained from patients with FMF during attacks and remission. The cytokine concentrations in plasma and in supernatants from whole blood stimulated by bacterial lipopolysaccharide (LPS) were determined. RESULTS: There were 27 patients with FMF, of whom 8 were studied during attacks, 9 during remission and 10 during both attack and remission. FMF attacks did not affect levels of plasma tumor necrosis factor-alpha (TNF-alpha) or interleukin 1beta (IL-1beta). In contrast, compared to remission, FMF attacks were associated with significantly higher mean levels of plasma IL-6 [8.4 pg/ml, 95% confidence interval (CI) 7.8-8.9 in remission vs 59 pg/ml, CI 21.4-96.7 during attacks; p=0.0005], sTNFr p55 (1.3 ng/ml, CI 1.2-1.4, vs 1.98 ng/ml, CI 1.6-2.3; p=0.005), and sTNFr p75 (2.9 ng/ml, CI 2.5-3.3, vs 4.09 ng/ml, CI 3.2-4.9; p=0.0249). The TNF-alpha, IL-1beta, and IL-6 content in supernatants derived from LPS stimulated blood cells was not modified by the attacks of FMF. Significant lower TNF-alpha release in LPS stimulated whole blood was detected in patients who were sampled in a later stage of the attacks (r=-0.54, p=0.047). CONCLUSION: Our results suggest that the cytokine network is activated during attacks of FMF. IL-6 appears to play an important role in the evolution of FMF attacks. Whether TNF-alpha or IL-1beta has a function in initiating the attacks remains to be established.

Acute Disease↗
PubMed1998

Multiple authorship: the contribution of senior authors.

CONTEXT: The number of authors per article has increased markedly in recent years. Little is known about the hierarchical order of authorship and its change over time. OBJECTIVE: To assess the change in number and profile of authors of original articles published over a 20-year period in BMJ. It was hypothesized that the number of authors increased over this 20-year period and that it was the senior scientists who benefited most. DESIGN: Comparative descriptive analysis of the number and academic rank of authors who published original articles in BMJ volumes 270 (1975), 280 (1980), 290 (1985), 300 (1990), and 310 (1995). MAIN OUTCOME MEASURES: The specific academic rank, order, and number of authors for each original article. Eight categories of authorship were distinguished as follows: 1, professor; 2, department chairperson; 3, consultant; 4, senior registrar; 5, lecturer and/or registrar; 6, medical student; 7, house officer; and 8, miscellaneous. RESULTS: The number of original articles published per year decreased from 262 (1975) to 125 (1995). The mean number (SD) of authors per article increased steadily from 3.21 (SD, 1.89) (1975) to 4.46 (SD, 2.04) (1995). Most authors belonged to category 3, and its proportion varied from 24.7% (1975) to 22.6% (1995), while category 1 grew from 13.2% to 20.3%. Category 5 authorship dropped from 24.3% (1975) to 15.8% (1995). With regard to first authorship, category 1 more than doubled from 8.0% (1975) to 16.8% (1995) compared with category 5 whose proportion decreased from 34.0% to 24.8%. Most last authors were from category 1, 20.4% (1975), growing to 29.0% (1995). CONCLUSION: Over the last 20 years the number of BMJ authors of original articles increased, mainly because of the rise of authorship among professors and department chairpersons.

Authorship↗