A novel indel NF1 mutation identified in a patient with neurofibromatosis type 1 / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To identify the genetic etiology in a Chinese patient with neurofibromatosis type 1 (NF-1).</p><p><b>METHODS</b>All coding exons and the flanking sequences of neurofibromin 1 (NF1) gene from the patient were captured, individually barcoded and subjected to HiSeq2000 high-throughput sequencing. Suspected mutation was validated in the nuclear family members with Sanger sequencing.</p><p><b>RESULTS</b>A novel indel mutation, c.789_790delAGinsT, was identified in the exon 8 of the NF1 gene in the patient but not in her asymptomatic parents. The mutation was predicted to have caused shifting of the reading frame and a premature downstream stop codon (p.K263Nfs*18). Two known polymorphisms, c.888+108 C>T (rs2953000) and c.888+118 G>T (rs2952999), was detected in the flanking of the indel mutation in the patient and her father. Sequencing chromatogram for the family indicates that above changes are located on the same chromosome.</p><p><b>CONCLUSION</b>The c.789_790delAGinsT, as a de novo mutation occurring on the paternally derived chromosome, is most likely to be causative for the disease. Compared with Sanger sequencing, targeted next-generation sequencing is more efficient and can dramatically reduce the cost for the genetic testing of NF-1.</p>