NF1 Molecular Characterization And Neurofibromatosis Type 1 Genotype-phenotype Correlations In Chinese Population

Background: To reveal the mutation spectrum and genotype-phenotype correlation in 109 Chinese patients suspicious for NF1 by molecular analysis, meanwhile establish effective detective methods for NF1 in Chinese Mainland.Methods: We screened 109 Chinese patients in 100 families with NF1-like phenotype(CALs, neurofibromas, etc.) by Sanger sequencing, c DNA sequencing and multiplex ligation-dependent probe amplification.Results: We identified the NF1 mutations in 97 individuals, among which 34 intragenic mutations have not been reported.Conclusions: Our exhaustive mutation analysis detects the mutation in 89%(89/100) of the overall NF1-likeprobandsand 93%(70/75) in those fulfilling the National Institutes of Health(NIH) criteria, characterizing a large spectrum of NF1 mutations in Chinese population. Upon which, it can enable the establishment of an optimized strategy in early diagnosis and genetic counseling for Chinese NF1 patients. Furthermore, our study indicates that those individuals only clinically present with multiple CALs have a big possibility(76%) of NF1 and show a significant low mutation rate(p<0.05) than those fulfilled the NIH criteria, which will provide a concept for the clinician that the multiple CALs group has a considerable possibility(24%) of being attributed to other comparable diseases. Furthermore, our study indicates: 1)Those individuals only clinically present with multiple CALs have a big possibility(76%) for NF1 and a considerable possibility(24%) of being attributed to other comparable diseases. 2)Exon 15 is prone to be a mutation hotspot.3)Lisch nodules is an extremely effective diagnosis criterion for NF1, especially for those over 6 years old.4)Anaemic nevi harbors the potential to be a new diagnostic criterion, etc.