Abstract
BackgroundNeurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by a heterozygous germline mutation in the tumor suppressor gene NF1. Because of the existence of highly homologous pseudogenes, the large size of the gene, and the heterogeneity of mutation types and positions, the detection of variations in NF1 is more difficult than that for an ordinary gene.MethodsIn this study, we collected samples from 23 patients among 46 study participants from 12 unrelated Chinese families with NF1. We used a combination of Sanger sequencing, targeted next-generation sequencing, and multiplex ligation-dependent probe amplification to identify potential mutations of different types.ResultsSeven recurrent mutations and four novel mutations were identified with the aforementioned methods, which were subsequently confirmed by either restriction fragment length polymorphism analysis or Sanger sequencing. Truncating mutations accounted for 73% (8/11) of all mutations identified. We also exhaustively investigated the clinical manifestations of NF1 in patients via acquired pathography, photographs and follow-up. However, no clear genotype–phenotype correlation has been found to date.ConclusionIn conclusion, the novel mutations identified broaden the spectrum of NF1 mutations in Chinese; however, obvious correlations between genotype and phenotype were not observed in this study.
Highlights
Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by a heterozygous germline mutation in the tumor suppressor gene NF1
Caused by a germline heterozygous mutation in the tumor suppressor gene neurofibromin 1 (NF1; MIM: 613113) located on chromosome 17q11.2, NF1 is characterized by typical café-au-lait spots and cutaneous neurofibromas [2]
Owing to its extremely frequent incidence of mutation without obvious mutational hot spots, over 2600 NF1 mutations have hitherto been reported in the Human Gene Mutation Database (HGMD)
Summary
Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by a heterozygous germline mutation in the tumor suppressor gene NF1. Because of the existence of highly homologous pseudogenes, the large size of the gene, and the heterogeneity of mutation types and positions, the detection of variations in NF1 is more difficult than that for an ordinary gene. Neurofibromatosis type 1 (NF1; MIM: 162200) is one of the most common autosomal dominant inherited diseases with an incidence of 1 in 2500–3000 individuals [1]. Caused by a germline heterozygous mutation in the tumor suppressor gene neurofibromin 1 (NF1; MIM: 613113) located on chromosome 17q11.2, NF1 is characterized by typical café-au-lait spots and cutaneous neurofibromas [2]. NF1 is one of the largest known genes with a genomic size of 282 kb, consisting of 57 constitutive exons and three alternatively spliced exons [5]. Single nucleotide substitutions and small deletions (20 bp or less) account for 71% of currently known mutations
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