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Neurofibromatosis type 1: a single center's experience in Korea

  • Kim, Min Jeong (Department of Pediatrics, Maryknoll Medical Center) ;
  • Cheon, Chong Kun (Department of Pediatrics, Pusan National University School of Medicine)
  • Received : 2013.12.03
  • Accepted : 2014.06.03
  • Published : 2014.09.10

Abstract

Purpose: Neurofibromatosis 1 (NF1) is an autosomal dominant condition caused by an NF1 gene mutation. NF1 is also a multisystem disorder that primarily affects the skin and nervous system. The goal of this study was to delineate the phenotypic characterization and assess the NF1 mutational spectrum in patients with NF1. Methods: A total of 42 patients, 14 females and 28 males, were enrolled in this study. Clinical manifestations and results of the genetic study were retrospectively reviewed. Results: Age of the patients at the time of NF1 diagnosis was $15.8{\pm}14.6$ years (range, 1-62 years). Twelve patients (28.6%) had a family history of NF1. Among the 42 patients, $Caf\acute{e}$-au-lait spots were shown in 42 (100%), neurofibroma in 31 (73.8%), freckling in 22 (52.4%), and Lisch nodules in seven (16.7%). The most common abnormal finding in the brain was hamartoma (20%). Mental retardation was observed in five patients (11.9%), seizures in one patient (2.4%), and plexiform neurofibromas (PNFs) in four patients (9.5%). One patient with PNFs died due to a malignant peripheral nerve sheath tumor in the chest cavity. Genetic analysis of seven patients identified six single base substitutions (three missense and three nonsense) and one small deletion. Among these mutations, five (71.4%) were novel (two missense mutations: p.Leu1773Pro, p.His1170Leu; two nonsense mutations: $p.Arg2517^*$, $p.Cys2371^*$; one small deletion: $p.Leu1944Phefs^*6$). Conclusion: The clinical characteristics of 42 Korean patients with NF1 were extremely variable and the mutations of the NF1 gene were genetically heterogeneous with a high mutation-detection rate.

Keywords

References

  1. Hersh JH; American Academy of Pediatrics Committee on Genetics. Health supervision for children with neurofibromatosis. Pediatrics 2008;121:633-42.
  2. Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med 2010;12:1-11.
  3. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol 1988;45:575-8.
  4. Sharif S, Upadhyaya M, Ferner R, Majounie E, Shenton A, Baser M, et al. A molecular analysis of individuals with neurofibromatosis type 1 (NF1) and optic pathway gliomas (OPGs), and an assessment of genotype-phenotype correlations. J Med Genet 2011;48:256-60.
  5. Prada CE, Rangwala FA, Martin LJ, Lovell AM, Saal HM, Schorry EK, et al. Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1. J Pediatr 2012;160:461-7.
  6. Chong JA, Moran MM, Teichmann M, Kaczmarek JS, Roeder R, Clapham DE. TATA-binding protein (TBP)-like factor (TLF) is a functional regulator of transcription: reciprocal regulation of the neurofibromatosis type 1 and c-fos genes by TLF/TRF2 and TBP. Mol Cell Biol 2005;25:2632-43.
  7. Young H, Hyman S, North K. Neurofibromatosis 1: clinical review and exceptions to the rules. J Child Neurol 2002;17:613-21.
  8. DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics 2000;105(3 Pt 1):608-14.
  9. Ledbetter DH, Rich DC, O'Connell P, Leppert M, Carey JC. Precise localization of NF1 to 17q11.2 by balanced translocation. Am J Hum Genet 1989;44:20-4.
  10. de Goede-Bolder A, Cnossen MH, Dooijes D, van den Ouweland AM, Niermeijer MF. From gene to disease; neurofibromatosis type 1. Ned Tijdschr Geneeskd 2001;145:1736-8.
  11. Cichowski K, Jacks T. NF1 tumor suppressor gene function: narrowing the GAP. Cell 2001;104:593-604.
  12. Valero MC, Pascual-Castroviejo I, Velasco E, Moreno F, Hernandez-Chico C. Identification of de novo deletions at the NF1 gene: no preferential paternal origin and phenotypic analysis of patients. Hum Genet 1997;99:720-6.
  13. Jeong SY, Park SJ, Kim HJ. The spectrum of NF1 mutations in Korean patients with neurofibromatosis type 1. J Korean Med Sci 2006;21:107-12.
  14. Ko JM, Sohn YB, Jeong SY, Kim HJ, Messiaen LM. Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofibromatosis type 1. Pediatr Neurol 2013;48:447-53.
  15. Khan AK, Deb S, Ray DK, Mandal SN, Mukhopadhaya S, Mandal S. Diffuse neurofibroma of scalp. Neurol India 2002;50:516-7.
  16. Grobmyer SR, Reith JD, Shahlaee A, Bush CH, Hochwald SN. Malignant peripheral nerve sheath tumor: molecular pathogenesis and current management considerations. J Surg Oncol 2008;97:340-9.
  17. Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 2002;39:311-4.
  18. Listernick R, Ferner RE, Liu GT, Gutmann DH. Optic pathway gliomas in neurofibromatosis-1: controversies and recommendations. Ann Neurol 2007;61:189-98.

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