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

研究成果: 雜誌貢獻文章同行評審

8 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號72
期刊Journal of Biomedical Science
25
發行號1
DOIs
出版狀態已發佈 - 十月 5 2018
對外發佈

Keywords

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

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 分子生物學
  • 臨床生物化學
  • 細胞生物學
  • 生物化學(醫學)
  • 藥學(醫學)

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