A Novel Frameshift Mutation in Neurofibromin 1 Gene in a Chinese Family with Neurofibromatosis Type 1

Abstract

The verification of subsequent two-directional sequencing revealed a heterozygous frameshift mutation, c.6547_6548insA (p.T2183NfsX38) on exon 42 in NF1 gene, identified in the proband and her affected progeny, but not in her spouse and 100 unrelated healthy controls [Figure 1]d. Moreover, the protein sequence alignment showed a high degree of conservation of the amino acid sequence around the T2183 residue in the neurofibromin protein across 12 different species by the UCSC Genome Bioinformatics tool [Figure 1]e. In addition, this NF1 mutation has not been included in the Human Gene Mutation Database (HGMD), the NF1 Leiden Open Variation Database, and literatures on PubMed. [...]it was considered a novel mutation. [1],[5] The NF1 is a tumor suppressor gene encoding a RAS GTPase-activating protein called neurofibromin, which is a large multi-domain 2818 amino acid protein. [5] Hitherto, more than 2000 various causative mutations of NF1 gene associated with NF1 have been recorded in the HGMD database including missense, nonsense, splice-site, and frameshift mutations. [5] Although the function of these two domains remains to be elucidated, multiple sequence alignment across 12 different species showed a high degree of conservation around the T2183 residue of the neurofibromin protein within this region [Figure 1]e, indicating its importance...