title: Identification of a novel mevalonate kinase gene mutation in combination with the common MVK V377I substitution and the low-penetrance TNFRSF1A R92Q mutation.
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 T(1132) --> 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.
authors.affiliation: Department of Infectious Diseases and Immunology, Children's Hospital, University of Munich, Germany. florian.hoffmann@med.uni-muenchen.de
authors.forename: Florian
authors.initials: F
authors.lastname: Hoffmann
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Silvia
authors.initials: S
authors.lastname: Stojanov
authors.forename: Yoon S
authors.initials: YS
authors.lastname: Shin
authors.forename: Ellen D
authors.initials: ED
authors.lastname: Renner
authors.forename: Anja
authors.initials: A
authors.lastname: Kéry
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zellerer
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Belohradsky
mesh_terms: D019943:Amino Acid Substitution; D002648:Child; D010505:Familial Mediterranean Fever / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics*; D007072:Immunoglobulin D / Q000378:metabolism; D019656:Loss of Heterozygosity; D009154:Mutation / Q000235:genetics*; D019683:Penetrance; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*
chemical_list: D007072:Immunoglobulin D; D047888:Receptors, Tumor Necrosis Factor, Type I; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase