Abstract:  Objective Neurofibromatosis type (NF) 1 is an autosomal dominant inherited disorder caused by NF1 gene mutation. The characteristics of NF 1 include multiple Café-au-lait spots, neurofibroma, freckling in the axillary or inguinal regions, Optic glioma, Lisch nodules and skeletal abnormalities. We analyzed NF1 gene in 8 cases with multiple Café-aulait spots in order to diagnose and understand clinical heterogeneity of NF1 in children. Methods Eight patients, 5 males and 3 females aged 1- 12 years, were selected from hospital during June 2013 to October 2015. All of them complained of multiple Café-au-lait macules since birth, and two were accompanied by plexiform neurofibromas, one with multiple cutaneous neurofibromas. All parents were non-consanguineous and asymptomatic. Variable Café-au-lait macules were found in 3 parents, one with multiple Café-au-lait spots, and the other two with 1-2 skin lesions. NF1 gene was studied by direct PCR sequencing and followed by MLPA analysis if the sequencing was negative. All patients had no echocardiography and ophthalmic examinations. Results Seven mutations were found in 8 patients, including complete NF1 deletion in 2 cases, 4 deletion mutations (c.4974_4977delCTAT, p.Y1659TfsX17, c.3987_3988delAG, p.S1329fsX4, c.1511delC, p.P504QfsX22 and c.6388delC, p.L2130fsX3), 1 splicing mutation (c.3975-2delA) and 1 nonsense mutation (c.3721C >?T,p.R1241X). The mutations were not found in the peripheral blood of all the parents. All mutations except large deletion and nonsense mutation were not reported. Conclusions Mutations in NF1 gene can cause NF 1. Multiple Café-au-lait macules may be the earliest clinical manifestation of NF1. NF1 gene analysis can be performed to confirm the diagnosis and provide necessary genetic counseling, even though there is no family history and other clinical abnormalities. In this study, there were 7 mutations found in 8 patients,5 of which were not  reported, all mutations were de novo.