The R1947X mutation of NF1 causing autosomal dominant neurofibromatosis type 1 in a Chinese family

a.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan 430074, China
b.
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
c.
Department of Dermatology, the First People's Hospital of Xian Tao City, Xiantao 433000, China

More Information

Corresponding author: E-mail address: lium@mail.hust.edu.cn (Mugen Liu)

Equally contributed to this work.

摘要

- /
- /
Abstract: Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor geneNF1, which encodes neurofibromin. The main function of neurofibromin is down-regulating the biological activity of the proto-oncoprotein Ras by acting as a Ras-specific GTPase activating protein. In this study, we identified a Chinese family affected with neurofibromatosis type 1. The known gene NF1 associated with NF1 was studied by linkage analysis and by direct sequencing of the entire coding region and exon-intron boundaries of the NF1 gene. The R1947X mutation of NF1 was identified, which was co-segregated with affected individuals in the Chinese family, but not present in unaffected family members. This is the first report, which states that the R1947X mutation of NF1 may be one of reasons for neurofibromatosis type 1 in Chinese population.
- neurofibromatosis type 1 /
- neurofibromin /
- R1947X mutation
Equally contributed to this work.
注释:

HTML全文

参考文献(24)

[1]	Andersen, L.B., Ballester, R., Marchuk, D.A. et al. Mol. Cell Biol., 13 (1993),pp. 487-495
[2]	Andrews, J.D., Mancini, D.N., Singh, S.M. et al. Hum. Mol. Genet., 5 (1996),pp. 503-507
[3]	Bonneau, F., D’Angelo, I., Welti, S. et al. Expression, purification and preliminary crystallographic characterization of a novel segment from the neurofibromatosis type 1 Acta Crystallogr D. Biol. Crystallogr., 60 (2004),pp. 2364-2367
[4]	Cichowski, K., Jacks, T. Cell, 104 (2001),pp. 593-604
[5]	Consoli, C., Moss, C., Green, S. et al. J. Invest. Dermatol., 125 (2005),pp. 463-466
[6]	D’Angelo, I., Welti, S., Bonneau, F. et al. A novel bipartite phospholipid-binding module in the neurofibro- matosis type 1 protein EMBO Rep., 7 (2006),pp. 174-179
[7]	Fahsold, R., Hoffmeyer, S., Mischung, C. et al. Am. J. Hum. Genet., 66 (2000),pp. 790-818
[8]	Gutmann, D.H., Aylsworth, A., Carey, J.C. et al. The diagnostic evaluation and multidisciplinary management of neurofibro- matosis 1 and neurofibromatosis 2 JAMA, 278 (1997),pp. 51-57
[9]	Hatori, M., Hosaka, M., Watanabe, M. et al. Osteosarcoma in a patient with neurofibromatosis type 1: A Case report and review of the literature Tohoku J. Exp. Med., 208 (2006),pp. 343-348
[10]	Jeong, S.Y., Park, S.J., Kim, H.J. J. Korean Med. Sci., 21 (2006),pp. 107-112
[11]	Krkljus, S., Abernathy, C.R., Johnson, J.S. et al. Analysis of CpG C-to-T mutations in neurofibromatosis type 1 Hum. Mutat., 11 (1998),pp. 411-422
[12]	Leppig, K.A., Kaplan, P., Viskochil, D. et al. Familial neurofibromatosis 1 microdeletions: Cosegregation with distinct facial phenotype and early onset of cutaneous neurofibromata Am. J. Med. Genet., 73 (1997),pp. 197-204
[13]	Origone, P., Bonioli, E., Panucci, E. et al. The Genoa experience of prenatal diagnosis in NF1 Prenat. Diagn., 20 (2000),pp. 719-724
[14]	Origone, P., De Luca, A., Bellini, C. et al. Hum. Mutat., 20 (2002),pp. 74-75
[15]	Park, K.C., Choi, H.O., Park, K.H. et al. J. Hum. Genet., 45 (2000),pp. 84-85
[16]	Riva, P., Corrado, L., Natacci, F. et al. NF1 microdeletion syndrome: Refined FISH characterization of sporadic and familial deletions with locus-specific probes Am. J. Hum. Genet., 66 (2000),pp. 100-109
[17]	Scheffzek, K., Ahmadian, M.R., Wiesmuller, L. et al. Structural analysis of the GAP-related domain from neurofibromin and its implications EMBO J., 17 (1998),pp. 4313-4327
[18]	Trovo-Marqui, A.B., Tajara, E.H. Neurofibromin: a general outlook Clin. Genet., 70 (2006),pp. 1-13
[19]	Vandenbroucke, I., Vandesompele, J., de Paepe, A. et al. Quantification of NF1 transcripts reveals novel highly expressed splice variants FEBS Lett., 522 (2002),pp. 71-76
[20]	Vandenbroucke, I., van Oostveldt, P., Coene, E. et al. Neurofibromin is actively transported to the nucleus FEBS Lett., 560 (2004),pp. 98-102
[21]	Wang, Q., Liu, M., Xu, C. et al. J. Mol. Med., 83 (2005),pp. 203-208
[22]	Welti, S., Fraterman, S., D’Angelo, I. et al. The sec14 homology module of neurofibromin binds cellular glycerophospholipids: mass spectrometry and structure of a lipid complex J. Mol. Biol., 366 (2007),pp. 551-562
[23]	Wu, B.L., Schneider, G.H., Korf, B.R. Am. J. Med. Genet., 69 (1997),pp. 98-101
[24]	Zhu, Y., Parada, L.F. Neurofibromin, a tumor suppressor in the nervous system Exp. Cell. Res., 264 (2001),pp. 19-28