Abstract
Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) is a recessively inherited recurrent fever syndrome. We describe a family of eldest son and monozygotic twin younger sisters with characteristic syndrome of HIDS, but normal level of IgD. Mevalonate kinase (MK) activity was deficient in all of them, and analysis of the MVK gene revealed compound heterozygosity for 2 new mutations, one of which was the disease-causing splicing mutation and the other was a novel missense mutation. All the patients had the same compound heterozygous mutations c.227-1 G > A and c.833 T > C, which resulted in exon 4 skipping and p.Val278Ala. This is the first case in which exon skipping mutation of the MVK gene has been certainly identified at the genomic DNA level. In each case, in which HIDS is clinically suspected, despite normal IgD level, analysis of MK activity and the MVK gene should be performed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
van der Meer JW, Vossen JM, Radl J, Van Nieuwkoop JA, Meyer CJ, Lobatto S et al (1984) Hyperimmunoglobulinaemia D and periodic fever: a new syndrome. Lancet 1:1087–1090
Church LD, Churchman SM, Hawkins PN, McDermott MF (2006) Hereditary auto-inflammatory disorders and biologics. Semin Immunopathol 27:494–508
Simon A, van der Meer JW (2007) Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes. Am J Physiol Regul Integr Comp Physiol 292:R86–R98
Fenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Duran M et al (2001) Clinical and molecular variability in childhood periodic fever with hyperimmunoglobuninaemia D. Rheumatology (Oxford) 40:579–584
Stojanov S, Lohse P, Lohse P, Hoffmann F, Renner ED, Zellerer S et al. (2004) Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the phenotype of hyperimmunoglobulinemia D with periodic fever syndrome or vice versa. Arthritis Rheum 50:1951–1958
Touitous I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C et al (2004) Infevers: an evolving mutation database for autoinflammatory syndromes. Hum Mutat 24:194–198
Pouchot J, Sampalis JS, Beaudet F, Carette S, Decary F, Salusinsky-Sternbach M et al (1991) Adult Still’s disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore) 70:118–136
Haas D, Hoffmann GF (2006) Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome. Orphanet J Rare Dis 1:13
Cuisset L, Drenth JP, Simon A, Vincent MF, Van der Velde Visser S, Van der Meer JW (2001) Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet 9(4):260–266
Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG et al (1999) Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet 22:178–181
Takada K, Aksentijevich I, Mahadevan V, Dean JA, Kelley RI, Kastner DL (2003) Favorable preliminary experience with etanercept in two patients with the hyperimmunoglobulinemia D and periodic fever syndrome. Arthritis Rheum 48:2645–2651
Drenth JP, Haagsma CJ, van der Meer JW (1994) Hyperimmunoglobulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients. International Hyper-IgD Study Group. Medicine (Bartimore) 73:133–144
Naruto T, Nakagishi Y, Mori M, Miyamae T, Imagawa T, Yokota S (2009) Hyper-IgD syndrome with novel mutation in Japanese girl. Mod Rheumatol 19(1):96–99
Acknowledgments
The authors thank Dr. Georg F. Hoffmann for measurement regarding the mevalonic kinase activity.
Conflict of interest
There is no financial or other potential conflict of interest for each author.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mizuno, T., Sakai, H., Nishikomori, R. et al. Novel mutations of MVK gene in Japanese family members affected with hyperimmunoglobulinemia D and periodic fever syndrome. Rheumatol Int 32, 3761–3764 (2012). https://doi.org/10.1007/s00296-011-2225-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-011-2225-z