Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome
| Autor: | Jacques S. Beckmann, Gilles Grateau, J.W.M. van der Meer, J.P.H. Drenth, J.G.N. de Jong, S.D. van der Velde-Visser, Laurence Cuisset, Christian Vasseur, Marc Delpech |
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| Rok vydání: | 1999 |
| Předmět: |
Genetics
Cytokines and febrile illnesses Mevalonate kinase deficiency Hyper-IgD syndrome Clinical description and delineation of genetic syndromes Familial Mediterranean fever Mevalonate kinase Inborn errors of metabolism Biology medicine.disease Muckle–Wells syndrome Familial Cold Autoinflammatory Syndrome TNF receptor associated periodic syndrome medicine biology.protein Stofwisselingsziekten Cytokinen en koortsende ziekten Erfelijke stofwisselingsziekten Periodic fever syndrome Klinische beschrijving en moleculaire definiëring van genetische syndromen |
| Zdroj: | Nature Genetics, 22, 178-181. Nature america inc Nature Genetics, 22, 178-181 Nature Genetics, 22, 2, pp. 178-181 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/9696 |
| Popis: | 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 lesions1. 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 obscure2,3,4. 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 receptor7,8,9,10. 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.I.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. |
| Databáze: | OpenAIRE |
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