Abstract
The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is an autosomal recessively inherited autoinflammatory disease caused by mutations in the mevalonate kinase (MVK) gene on chromosome 12q24, which lead to a depressed enzymatic activity of mevalonate kinase (MK). TNF-receptor associated periodic syndrome (TRAPS), on the other hand, is the most frequent autosomal dominantly inherited periodic fever syndrome due to mutations in exons 2–4 and 6 of the TNFRSF1A gene on chromosome 12p13.2. We describe a girl with heterozygosity for the common MVK V377I mutation and for a novel T1132 → C transition, leading to the exchange of serine (TCC) by proline (CCC) at amino-acid position 378. Interestingly, our patient presented only with mild clinical features typical of HIDS and slightly increased immunoglobulin D levels, but a distinctly diminished MK activity. The girl was also heterozygous for the TNFRSF1A R92Q low-penetrance mutation, which may have significant proinflammatory effects. However, at the time of presentation, the patient had no TRAPS-associated symptoms.
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Hoffmann, F., Lohse, P., Stojanov, S. et al. Identification of a novel mevalonate kinase gene mutation in combination with the common MVK V377I substitution and the low-penetrance TNFRSF1A R92Q mutation. Eur J Hum Genet 13, 510–512 (2005). https://doi.org/10.1038/sj.ejhg.5201352
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DOI: https://doi.org/10.1038/sj.ejhg.5201352
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