title: Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1.
abstract: Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of café-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions. In the present study, we have used a combination of techniques (heteroduplex analysis, sequencing, loss of heterozygosity and quantification of gene dosage) to define the genetic defect in 68 individuals from a cohort of 107 NF1 Taiwanese patients of Chinese origin. Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frame-shift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature. The detection rate with the various analytical techniques and the types of mutation detected are consistent with published data involving both individuals and large cohort studies from other ethnic backgrounds.
authors.affiliation: Department of Medical Genetics, National Taiwan University School of Medicine, Taipei, Taiwan. mjlee@ha.mc.ntu.edu.tw
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: You
authors.forename: Shinn-Chong
authors.initials: SC
authors.lastname: Chiou
authors.forename: Li-Chu
authors.initials: LC
authors.lastname: Lin
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.forename: Wang-Chao
authors.initials: WC
authors.lastname: Lee
authors.forename: Wu-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Fon-Jou
authors.initials: FJ
authors.lastname: Hsieh
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Stephenson
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002681:China; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D016514:Genes, Neurofibromatosis 1; D020180:Heteroduplex Analysis; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics*; D022821:RNA Splice Sites
chemical_list: D022821:RNA Splice Sites