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TNFRSF1A and MEFV mutations in childhood onset multiple sclerosis.
Eur J Paediatr Neurol 2018; 22(1):72-81EJ

Abstract

To investigate frequency and phenotype of TNFRSF1A and MEFV mutations in childhood-onset multiple sclerosis (MS). Twenty-nine clinically well characterized patients were investigated for mutations in exons 2, 3, 4, and 6 of the TNFRSF1A gene and in exons 2, 3, 9, 10 of the MEFV gene. Standardized morbidity ratio (SMR) was used to assess whether the number of observed mutations was higher than expected. Eleven out of 29 patients tested positive for mutations. Heterozygosity for the TNFRSF1A R92Q (rs4149584) variant was found in 6/11 mutation-positive patients. The SMR for R92Q in our pediatric MS population was 4.6 (95% CI 1.7-10.0), 7.0 (95% CI 2.6-15.2), and 13.6 (95% CI 5.0-29.7), depending on reference population. Six patients carried at least one heterozygous MEFV mutation with SMRs of 21.4 (95% CI 7.9-46.6) and 14.6 (95% CI 5.4-31.9). Clinical characteristics of childhood MS patients with or without mutations did not differ significantly. Conclusion One third of our childhood MS patients had a heterozygous mutation in the TNFRSF1A and/or MEFV gene. This proportion by far exceeds the number of mutations expected and was higher than in adult MS patients, suggesting that these mutations might contribute to the pathogenesis of childhood MS.

Authors+Show Affiliations

Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, Lindwurmstraβe 4, D-80337 München, Ludwig-Maximillian's University, Germany. Electronic address: astrid.blaschek@med.uni-muenchen.de.Institute of Social Paediatrics and Adolescent Medicine, Haydenstr 5, 80336 München, Ludwig-Maximillian's University, Germany. Electronic address: ruediger.kries@med.uni-muenchen.de.Hohentwielstr. 32, 78250 Tengen, Germany. Electronic address: pia.lohse@gmx.de.Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, Lindwurmstraβe 4, D-80337 München, Ludwig-Maximillian's University, Germany. Electronic address: kristina.huss@med.uni-muenchen.de.Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, Lindwurmstraβe 4, D-80337 München, Ludwig-Maximillian's University, Germany. Electronic address: katharina.vill@med.uni-muenchen.de.Dr. von Hauner Children's Hospital, Lindwurmstraβe 4, D-80337 München, Ludwig-Maximillian's University, Germany. Electronic address: bernd.belohradsky@yahoo.com.Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, Lindwurmstraβe 4, D-80337 München, Ludwig-Maximillian's University, Germany. Electronic address: florian.heinen@med.uni-muenchen.de.Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, Lindwurmstraβe 4, D-80337 München, Ludwig-Maximillian's University, Germany. Electronic address: wolfgang.mueller-felber@med.uni-muenchen.de.Institute of Clinical Neuroimmunology, Marchioninistraβe 15, 81377 München, Ludwig-Maximillian's University, Munich, Germany. Electronic address: tania.kuempfel@med.uni-muenchen.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28927886

Citation

Blaschek, Astrid, et al. "TNFRSF1A and MEFV Mutations in Childhood Onset Multiple Sclerosis." European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society, vol. 22, no. 1, 2018, pp. 72-81.
Blaschek A, V Kries R, Lohse P, et al. TNFRSF1A and MEFV mutations in childhood onset multiple sclerosis. Eur J Paediatr Neurol. 2018;22(1):72-81.
Blaschek, A., V Kries, R., Lohse, P., Huss, K., Vill, K., Belohradsky, B. H., ... Kümpfel, T. (2018). TNFRSF1A and MEFV mutations in childhood onset multiple sclerosis. European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society, 22(1), pp. 72-81. doi:10.1016/j.ejpn.2017.08.007.
Blaschek A, et al. TNFRSF1A and MEFV Mutations in Childhood Onset Multiple Sclerosis. Eur J Paediatr Neurol. 2018;22(1):72-81. PubMed PMID: 28927886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNFRSF1A and MEFV mutations in childhood onset multiple sclerosis. AU - Blaschek,Astrid, AU - V Kries,Rüdiger, AU - Lohse,Peter, AU - Huss,Kristina, AU - Vill,Katharina, AU - Belohradsky,Bernd H, AU - Heinen,Florian, AU - Müller-Felber,Wolfgang, AU - Kümpfel,Tania, Y1 - 2017/09/01/ PY - 2016/06/02/received PY - 2017/03/19/revised PY - 2017/08/21/accepted PY - 2017/9/21/pubmed PY - 2018/6/29/medline PY - 2017/9/21/entrez KW - Childhood KW - FMF KW - Familial Mediterranean fever KW - Multiple sclerosis KW - TRAPS KW - Tumor necrosis factor receptor 1-associated periodic syndrome SP - 72 EP - 81 JF - European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society JO - Eur. J. Paediatr. Neurol. VL - 22 IS - 1 N2 - To investigate frequency and phenotype of TNFRSF1A and MEFV mutations in childhood-onset multiple sclerosis (MS). Twenty-nine clinically well characterized patients were investigated for mutations in exons 2, 3, 4, and 6 of the TNFRSF1A gene and in exons 2, 3, 9, 10 of the MEFV gene. Standardized morbidity ratio (SMR) was used to assess whether the number of observed mutations was higher than expected. Eleven out of 29 patients tested positive for mutations. Heterozygosity for the TNFRSF1A R92Q (rs4149584) variant was found in 6/11 mutation-positive patients. The SMR for R92Q in our pediatric MS population was 4.6 (95% CI 1.7-10.0), 7.0 (95% CI 2.6-15.2), and 13.6 (95% CI 5.0-29.7), depending on reference population. Six patients carried at least one heterozygous MEFV mutation with SMRs of 21.4 (95% CI 7.9-46.6) and 14.6 (95% CI 5.4-31.9). Clinical characteristics of childhood MS patients with or without mutations did not differ significantly. Conclusion One third of our childhood MS patients had a heterozygous mutation in the TNFRSF1A and/or MEFV gene. This proportion by far exceeds the number of mutations expected and was higher than in adult MS patients, suggesting that these mutations might contribute to the pathogenesis of childhood MS. SN - 1532-2130 UR - https://www.unboundmedicine.com/medline/citation/28927886/TNFRSF1A_and_MEFV_mutations_in_childhood_onset_multiple_sclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3798(17)31860-3 DB - PRIME DP - Unbound Medicine ER -