scholarly journals The investigation for potential modifier genes in patients with neurofibromatosis type 1 based on next-generation sequencing

2018 ◽  
Vol Volume 11 ◽  
pp. 919-932 ◽  
Author(s):  
Fan Yang ◽  
Song Xu ◽  
Renwang Liu ◽  
Tao Shi ◽  
Xiongfei Li ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Modifier Genes ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Next generation sequencing identified a novel multi exon deletion of the NF1 gene in a Chinese pedigree with neurofibromatosis type 1

2018 ◽  
Vol 21 (2) ◽  
pp. 45-48
Author(s):  
J Yang ◽  
J-X An ◽  
X-L Liu ◽  
Z-Q Wang ◽  
G-M Xie ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Whole Body ◽  
Next Generation ◽  
Facial Region ◽  
Café Au Lait Spots ◽  
Generation Sequencing ◽  
Exon Deletion

AbstractNeurofibromatosis type 1 (NF1) is a genetic disease involving neurocutaneous abnormalities. Neurofibromatosis type 1 is an autosomal dominant disorder characterized by the neurofibromas and café-au-lait spots. Mutation in theNF 1gene causes NF1. TheNF 1gene encodes neurofibromin. In this study, we found a 31-year-old Chinese boy with NF1. He presented only with café-au-lait spots over the whole body. The proband’s mother had a severe phenotype with neurofibroma and café-au-lait macules over her whole body, mostly in the facial region. A novel multi exon deletion c.(4661+1_4662-1)_(5748+1_5749-1)del; [EX36_39DEL] on theNF 1gene has been identified in the proband. Quantitative real-time polymerase chain reaction (qPCR) confirmed that this mutation is co-segregated well and was inherited from the proband’s mother. The mutation was absent in the proband’s father and normal individuals. The novel multi exon deletion results in the formation of a truncated NF1 protein that caused the NF1 phenotype in this family. Our present study also emphasized the significance of rapid, accurate and cost-effective screening for the patient with NF1 by next generation sequencing (NGS).

scholarly journals The Use of Next-Generation Sequencing in Molecular Diagnosis of Neurofibromatosis Type 1: A Validation Study

2014 ◽  
Vol 18 (11) ◽  
pp. 722-735 ◽  
Author(s):  
Ryo Maruoka ◽  
Toshiki Takenouchi ◽  
Chiharu Torii ◽  
Atsushi Shimizu ◽  
Kumiko Misu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Validation Study ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Next-Generation Sequencing Reveals ThatHLA-DRB3,-DRB4, and-DRB5May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes

Diabetes ◽  
2016 ◽  
Vol 65 (3) ◽  
pp. 710-718 ◽  
Author(s):  
Lue Ping Zhao ◽  
Shehab Alshiekh ◽  
Michael Zhao ◽  
Annelie Carlsson ◽  
Helena Elding Larsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Islet Autoantibodies ◽  
Next Generation ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type ◽  
Generation Sequencing

scholarly journals Next-generation panel sequencing identifies NF1 germline mutations in three patients with pheochromocytoma but no clinical diagnosis of neurofibromatosis type 1

2018 ◽  
Vol 178 (2) ◽  
pp. K1-K9 ◽  
Author(s):  
Laura Gieldon ◽  
Jimmy Rusdian Masjkur ◽  
Susan Richter ◽  
Roland Därr ◽  
Marcos Lahera ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Clinical Diagnosis ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Next Generation ◽  
Medullary Thyroid

Objective Our objective was to improve molecular diagnostics in patients with hereditary pheochromocytoma and paraganglioma (PPGL) by using next-generation sequencing (NGS) multi-gene panel analysis. Derived from this study, we here present three cases that were diagnosed with NF1 germline mutations but did not have a prior clinical diagnosis of neurofibromatosis type 1 (NF1). Design We performed genetic analysis of known tumor predisposition genes, including NF1, using a multi-gene NGS enrichment-based panel applied to a total of 1029 PPGL patients. We did not exclude genes known to cause clinically defined syndromes such as NF1 based on missing phenotypic expression as is commonly practiced. Methods Genetic analysis was performed using NGS (TruSight Cancer Panel/customized panel by Illumina) for analyzing patients’ blood and tumor samples. Validation was carried out by Sanger sequencing. Results Within our cohort, three patients, who were identified to carry pathogenic NF1 germline mutations, attracted attention, since none of the patients had a clinical suspicion of NF1 and one of them was initially suspected to have MEN2A syndrome due to co-occurrence of a medullary thyroid carcinoma. In these cases, one splice site, one stop and one frameshift mutation in NF1 were identified. Conclusions Since phenotypical presentation of NF1 is highly variable, we suggest analysis of the NF1 gene also in PPGL patients who do not meet diagnostic NF1 criteria. Co-occurrence of medullary thyroid carcinoma and PPGL was found to be a clinical decoy in NF1 diagnostics. These observations underline the value of multi-gene panel NGS for PPGL patients.

scholarly journals Duodenal-Jejunal Flexure GI Stromal Tumor Frequently Heralds Somatic NF1 and Notch Pathway Mutations

2017 ◽  
pp. 1-12 ◽  
Author(s):  
Adam M. Burgoyne ◽  
Martina De Siena ◽  
Maha Alkhuziem ◽  
Chih-Min Tang ◽  
Benjamin Medina ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Notch Pathway ◽  
Neurofibromatosis Type ◽  
Incomplete Penetrance ◽  
Genomic Alterations ◽  
Single Nucleotide ◽  
Anatomic Distribution ◽  
Gi Stromal Tumor ◽  
Generation Sequencing

Purpose GI stromal tumors (GISTs) are commonly associated with somatic mutations in KIT and PDGFRA. However, a subset arises from mutations in NF1, most commonly associated with neurofibromatosis type 1. We define the anatomic distribution of NF1 alterations in GIST. Methods We describe the demographic/clinicopathologic features of 177 patients from two institutions whose GISTs underwent next-generation sequencing of ≥ 315 cancer-related genes. Results We initially identified six (9.7%) of 62 GISTs with NF1 genomic alterations from the first cohort. Of these six patients, five (83.3%) had unifocal tumors at the duodenal-jejunal flexure (DJF). Two additional patients with DJF GISTs had non- NF1 ( KIT and BRAF) genomic alterations. After excluding one DJF GIST with an NF1 single nucleotide polymorphism, four (57.1%) of seven sequenced DJF tumors demonstrated deleterious NF1 alterations, whereas only one (1.8%) of 55 sequenced non-DJF GISTs had a deleterious NF1 somatic mutation ( P < .001). One patient with DJF GIST had a germline NF1 variant that was associated with incomplete penetrance of clinical neurofibromatosis type 1 features along with a somatic NF1 mutation. Of the five DJF GISTs with any NF1 alteration, three (60%) had KIT mutations, and three (60%) had Notch pathway mutations ( NOTCH2, MAML2, CDC73). We validated these findings in a second cohort of 115 GISTs, where two (40%) of five unifocal NF1-mutated GISTs arose at the DJF, and one of these also had a Notch pathway mutation ( EP300). Conclusion Broad genomic profiling of adult GISTs has revealed that NF1 alterations are enriched in DJF GISTs. These tumors also may harbor concurrent activating KIT and/or inactivating Notch pathway mutations. In some cases, germline NF1 genetic testing may be appropriate for patients with DJF GISTs.

Prenatal Diagnosis of Tyrosinemia Type 1 Using Next Generation Sequencing

2016 ◽  
Vol 35 (4) ◽  
pp. 282-285 ◽  
Author(s):  
Maryam Rafati ◽  
Faezeh Mohamadhashem ◽  
Azadeh Hoseini ◽  
Somayeh Darzi Ramandi ◽  
Saeed Reza Ghaffari
Keyword(s):  
Prenatal Diagnosis ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Tyrosinemia Type 1 ◽  
Generation Sequencing
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