Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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A familial case of Blau syndrome caused by a novel NOD2 genetic mutation

  • Kim, Woojoong (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Park, Eujin (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Ahn, Yo Han (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Lee, Jiwon M. (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kang, Hee Gyung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Byung Joo (Department of Pediatrics, Inje University Haeundae Paik Hospital) ;
  • Ha, Il-Soo (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Cheong, Hae Il (Department of Pediatrics, Seoul National University College of Medicine)
  • 투고 : 2015.08.12
  • 심사 : 2015.11.26
  • 발행 : 2016.11.15
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초록

Blau syndrome (BS) is a rare autosomal dominant, inflammatory syndrome that is characterized by the clinical triad of granulomatous dermatitis, symmetric arthritis, and recurrent uveitis. Mutations in the nucleotide oligomerization domain 2 (NOD2 ) gene are responsible for causing BS. To date, up to 30 Blau-associated genetic mutations have been identified within this gene. We report a novel NOD2 genetic mutation that causes BS. A girl, aged 8 years, and her brother, aged 10 years, developed erythematous skin rashes and uveitis. The computed tomography angiogram of the younger sister showed features of midaortic dysplastic syndrome. The brother had more prominent joint involvement than the sister. Their father (38 years) was also affected by uveitis; however, only minimal skin involvement was observed in his case. The paternal aunt (39 years) and her daughter (13 years) were previously diagnosed with sarcoidosis. Mutational analysis revealed a novel c.1439 A>G mutation in the NOD2 gene in both siblings. The novel c.1439 A>G mutation in the NOD2 gene was found in a familial case of BS. Although BS is rare, it should always be considered in patients presenting with sarcoidosis-like features at a young age. Early diagnosis of BS and prompt multisystem workup including the eyes and joints can improve the patient's outcome.

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참고문헌

  1. Blau EB. Familial granulomatous arthritis, iritis, and rash. J Pediatr 1985;107:689-93. https://doi.org/10.1016/S0022-3476(85)80394-2
  2. Kanazawa N, Okafuji I, Kambe N, Nishikomori R, Nakata-Hizume M, Nagai S, et al. Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood 2005;105:1195-7.
  3. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nat Genet 2001;29:19-20. https://doi.org/10.1038/ng720
  4. Stenson PD, Mort M, Ball EV, Shaw K, Phillips A, Cooper DN. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet 2014;133:1-9. https://doi.org/10.1007/s00439-013-1358-4
  5. BIOBASE Biological Databases. Human gene mutation database (HGMD professional) [Internet]. Waltham (MA): BIOBASE Biological Databases; c2016 [cited 2015 Sep 25]. Available from: http://www.biobase-international.com/hgmd.
  6. Son S, Lee J, Woo CW, Kim I, Kye Y, Lee K, et al. Altered cytokine profiles of mononuclear cells after stimulation in a patient with Blau syndrome. Rheumatol Int 2010;30:1121-4. https://doi.org/10.1007/s00296-009-1342-4
  7. Lee Y, Lee JJ, Kim S, Lee SC, Han J, Heu W, et al. Dissecting the critical factors for thermodynamic stability of modular proteins using molecular modeling approach. PLoS One 2014;9:e98243. https://doi.org/10.1371/journal.pone.0098243
  8. Rose CD, Wouters CH, Meiorin S, Doyle TM, Davey MP, Rosenbaum JT, et al. Pediatric granulomatous arthritis: an international registry. Arthritis Rheum 2006;54:3337-44. https://doi.org/10.1002/art.22122
  9. Caso F, Costa L, Rigante D, Vitale A, Cimaz R, Lucherini OM, et al. Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis. Autoimmun Rev 2014;13:1220-9. https://doi.org/10.1016/j.autrev.2014.08.010
  10. Chamaillard M, Philpott D, Girardin SE, Zouali H, Lesage S, Chareyre F, et al. Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci USA 2003;100:3455-60. https://doi.org/10.1073/pnas.0530276100
  11. Ting SS, Ziegler J, Fischer E. Familial granulomatous arthritis (Blau syndrome) with granulomatous renal lesions. J Pediatr 1998;133:450-2. https://doi.org/10.1016/S0022-3476(98)70286-0
  12. Emaminia A, Nabavi M, Mousavi Nasab M, Kashef S. Central nervous system involvement in Blau syndrome: a new feature of the syndrome? J Rheumatol 2007;34:2504-5.
  13. Mourad F, Tang A. Sinus of valsalva aneurysm in Blau's syndrome. J Cardiothorac Surg 2010;5:16. https://doi.org/10.1186/1749-8090-5-16
  14. Arostegui JI, Arnal C, Merino R, Modesto C, Antonia Carballo M, Moreno P, et al. NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum 2007;56:3805-13. https://doi.org/10.1002/art.22966
  15. Okada S, Konishi N, Tsumura M, Shirao K, Yasunaga S, Sakai H, et al. Cardiac infiltration in early-onset sarcoidosis associated with a novel heterozygous mutation, G481D, in CARD15. Rheumatology (Oxford) 2009;48:706-7. https://doi.org/10.1093/rheumatology/kep061