Genetic diagnosis of neurofibromatosis type 1: targeted next- generation sequencing with Multiple Ligation-Dependent Probe Amplification analysis.
J Biomed Sci
; 25(1): 72, 2018 Oct 05.
Article
en En
| MEDLINE
| ID: mdl-30290804
ABSTRACT
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pruebas Genéticas
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Genes de Neurofibromatosis 1
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Neurofibromatosis 1
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Male
País/Región como asunto:
Asia
Idioma:
En
Año:
2018
Tipo del documento:
Article