Genetic diagnosis of neurofibromatosis type 1: Targeted next- generation sequencing with Multiple Ligation-Dependent Probe Amplification analysis

Yah Huei Wu-Chou, Tzu Chao Hung, Yin Ting Lin, Hsing Wen Cheng, Ju Li Lin, Chih Hung Lin, Chung Chih Yu, Kuo Ting Chen, Tu Hsueh Yeh, Yu Ray Chen

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1 Citation (Scopus)


Background: Neurofibromatosis type 1 (NF1) is a dominantly inherited tumor predisposition syndrome that targets the peripheral nervous system. It is caused by mutations of the NF1 gene which serve as a negative regulator of the cellular Ras/MAPK (mitogen-activated protein kinases) signaling pathway. Owing to the complexity in some parts of clinical diagnoses and the need for better understanding of its molecular relationships, a genetic characterization of this disorder will be helpful in the clinical setting. Methods: In this study, we present a customized targeted gene panel of NF1/KRAS/BRAF/p53 and SPRED1 genes combined with Multiple Ligation-Dependent Probe Amplification analysis for the NF1 mutation screening in a cohort of patients clinically suspected as NF1. Results: In this study, we identified 73 NF1 mutations and two BRAF novel variants from 100 NF1 patients who were suspected as having NF1. These genetic alterations are heterogeneous and distribute in a complicated way without clustering in either cysteine-serine-rich domain or within the GAP-related domain. We also detected fifteen multi-exon deletions within the NF1 gene by MLPA Analysis. Conclusions: Our results suggested that a genetic screening using a NGS panel with high coverage of Ras-signaling components combined with Multiple Ligation-Dependent Probe Amplification analysis will enable differential diagnosis of patients with overlapping clinical features.

Original languageEnglish
Article number72
JournalJournal of Biomedical Science
Issue number1
Publication statusPublished - Oct 5 2018
Externally publishedYes



  • Genetic counseling
  • MLPA
  • Neurofibromatosis type 1
  • RASopathies
  • Targeted NGS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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