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.