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Phenotypic expression of a spectrum of Neurofibromatosis Type 1 (NF1) mutations identified through NGS and MLPA
Phenotypic expression of a spectrum of Neurofibromatosis Type 1 (NF1) mutations identified through NGS and MLPA
- Source :
- Journal of the Neurological Sciences. 395:95-105
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Neurofibromatosis Type 1 (NF1) is caused by mutations of the NF1 gene. The aim of this study was to identify the genetic causes underlying the disease, attempt possible phenotype/genotype correlations and add to the NF1 mutation spectrum. A screening protocol based on genomic DNA was established in 168 patients, encompassing sequencing of all coding exons and adjoining introns using a custom targeted next generation sequencing protocol and subsequent confirmation of findings with Sanger sequencing. MLPA was used to detect deletions/duplications and positive findings were confirmed by RNA analysis. All novel findings were evaluated according to ACMG Standards and guidelines for the interpretation of sequence variants with the aid of in-silico bioinformatic tools and family segregation analysis. A germline variant was identified in 145 patients (86%). In total 49 known and 70 novel variants in coding and non-coding regions were identified. Seven patients carried whole or partial gene deletions. NF1 patients, present with high phenotypic variability even in cases where the same germline disease causing variant has been identified. Our findings will contribute to a better knowledge of the genetic causes and the phenotypic expression related to the disease.
- Subjects :
- Adult
Male
0301 basic medicine
Neurofibromatosis 1
Adolescent
Biology
DNA sequencing
Young Adult
03 medical and health sciences
Exon
symbols.namesake
Genotype
medicine
Humans
Computer Simulation
Genetic Testing
Multiplex ligation-dependent probe amplification
Neurofibromatosis
Child
Gene
Genetic Association Studies
Genetics
Sanger sequencing
Neurofibromin 1
Computational Biology
High-Throughput Nucleotide Sequencing
Infant
Middle Aged
medicine.disease
genomic DNA
Phenotype
030104 developmental biology
Neurology
Child, Preschool
Mutation
symbols
Female
Neurology (clinical)
Multiplex Polymerase Chain Reaction
Subjects
Details
- ISSN :
- 0022510X
- Volume :
- 395
- Database :
- OpenAIRE
- Journal :
- Journal of the Neurological Sciences
- Accession number :
- edsair.doi.dedup.....5de8ba45fffab83d3c6f2abf48a45c8b
- Full Text :
- https://doi.org/10.1016/j.jns.2018.10.006