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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

Authors :
Eleftheria Kokkinou
Maria Tzetis
Irene Fylaktou
Konstantina Kosma
Myrto Poulou
Sofia Kitsiou-Tzeli
Maria Tsipi
Helen Fryssira
Maria-Roser Pons
Eirini Tsoutsou
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.

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