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Late-onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation.

Abstract

OBJECTIVE

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominantly inherited autoinflammatory disorder caused by mutations in the TNFRSF1A gene. It is characterized by episodes of autoinflammation usually associated with fever, abdominal pain, myalgia, exanthema, arthralgia/arthritis, and ocular involvement. We undertook this study to investigate the prevalence of TRAPS in patients with multiple sclerosis (MS) who reported, in addition to their neurologic symptoms, at least 2 other symptoms compatible with TRAPS.

METHODS

Twenty-five unrelated MS patients were prospectively screened for TNFRSF1A mutations. In addition, blood samples from 365 unrelated MS patients and 407 unrelated Caucasian controls were analyzed to determine the R92Q carrier frequency.

RESULTS

Six of 25 adult MS patients (24%) with symptoms suggestive of TRAPS were found to carry the identical arginine-to-glutamine substitution at amino acid position 92 (R92Q or p.Arg121Gln) encoded by exon 4 of the TNFRSF1A gene. All R92Q heterozygotes had similar symptoms, including arthralgias/arthritis, myalgias, urticarial rash, and severe fatigue, which began before the onset of MS. In 5 of the 6 patients, we could identify family members who had TRAPS symptoms and had inherited the identical mutation. The R92Q exchange was also detected in 17 of 365 unselected MS patients (4.66%) and in 12 of 407 controls (2.95%) (P = 0.112). Three patients were heterozygous carriers of MEFV variants, in 1 patient in combination with the R92Q mutation.

CONCLUSION

Autoinflammatory syndromes and especially late-onset TRAPS should be considered in MS patients who report symptoms such as arthralgias/arthritis, myalgias, urticarial rash, and severe fatigue.

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  • Authors+Show Affiliations

    ,

    Institute of Clinical Neuroimmunology-Grosshadern, Ludwig-Maximilian-University of Munich, Marchioninistrasse 15, D-81377 Munich, Germany. tania.kuempfel@med.uni-muenchen.de

    , , , , ,

    Source

    Arthritis and rheumatism 56:8 2007 Aug pg 2774-83

    MeSH

    Adult
    Arginine
    Diagnosis, Differential
    Familial Mediterranean Fever
    Female
    Genetic Predisposition to Disease
    Genetic Testing
    Glutamine
    Heterozygote
    Humans
    Hypergammaglobulinemia
    Male
    Middle Aged
    Multiple Sclerosis
    Mutation
    Pedigree
    Prospective Studies
    Receptors, Tumor Necrosis Factor, Type I

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17665448

    Citation

    Kümpfel, Tania, et al. "Late-onset Tumor Necrosis Factor Receptor-associated Periodic Syndrome in Multiple Sclerosis Patients Carrying the TNFRSF1A R92Q Mutation." Arthritis and Rheumatism, vol. 56, no. 8, 2007, pp. 2774-83.
    Kümpfel T, Hoffmann LA, Rübsamen H, et al. Late-onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation. Arthritis Rheum. 2007;56(8):2774-83.
    Kümpfel, T., Hoffmann, L. A., Rübsamen, H., Pöllmann, W., Feneberg, W., Hohlfeld, R., & Lohse, P. (2007). Late-onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation. Arthritis and Rheumatism, 56(8), pp. 2774-83.
    Kümpfel T, et al. Late-onset Tumor Necrosis Factor Receptor-associated Periodic Syndrome in Multiple Sclerosis Patients Carrying the TNFRSF1A R92Q Mutation. Arthritis Rheum. 2007;56(8):2774-83. PubMed PMID: 17665448.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Late-onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation. AU - Kümpfel,Tania, AU - Hoffmann,Lisa-Ann, AU - Rübsamen,Heike, AU - Pöllmann,Walter, AU - Feneberg,Wolfgang, AU - Hohlfeld,Reinhard, AU - Lohse,Peter, PY - 2007/8/1/pubmed PY - 2007/9/19/medline PY - 2007/8/1/entrez SP - 2774 EP - 83 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 56 IS - 8 N2 - OBJECTIVE: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominantly inherited autoinflammatory disorder caused by mutations in the TNFRSF1A gene. It is characterized by episodes of autoinflammation usually associated with fever, abdominal pain, myalgia, exanthema, arthralgia/arthritis, and ocular involvement. We undertook this study to investigate the prevalence of TRAPS in patients with multiple sclerosis (MS) who reported, in addition to their neurologic symptoms, at least 2 other symptoms compatible with TRAPS. METHODS: Twenty-five unrelated MS patients were prospectively screened for TNFRSF1A mutations. In addition, blood samples from 365 unrelated MS patients and 407 unrelated Caucasian controls were analyzed to determine the R92Q carrier frequency. RESULTS: Six of 25 adult MS patients (24%) with symptoms suggestive of TRAPS were found to carry the identical arginine-to-glutamine substitution at amino acid position 92 (R92Q or p.Arg121Gln) encoded by exon 4 of the TNFRSF1A gene. All R92Q heterozygotes had similar symptoms, including arthralgias/arthritis, myalgias, urticarial rash, and severe fatigue, which began before the onset of MS. In 5 of the 6 patients, we could identify family members who had TRAPS symptoms and had inherited the identical mutation. The R92Q exchange was also detected in 17 of 365 unselected MS patients (4.66%) and in 12 of 407 controls (2.95%) (P = 0.112). Three patients were heterozygous carriers of MEFV variants, in 1 patient in combination with the R92Q mutation. CONCLUSION: Autoinflammatory syndromes and especially late-onset TRAPS should be considered in MS patients who report symptoms such as arthralgias/arthritis, myalgias, urticarial rash, and severe fatigue. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/17665448/Late_onset_tumor_necrosis_factor_receptor_associated_periodic_syndrome_in_multiple_sclerosis_patients_carrying_the_TNFRSF1A_R92Q_mutation_ L2 - https://doi.org/10.1002/art.22795 DB - PRIME DP - Unbound Medicine ER -