scholarly journals Performance Evaluation of SpliceAI for the Prediction of Splicing of NF1 Variants

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1308
Author(s):  
Changhee Ha ◽  
Jong-Won Kim ◽  
Ja-Hyun Jang
Keyword(s):  
Dna Sequencing ◽  
Sensitivity And Specificity ◽  
In Silico ◽  
Genetic Disorders ◽  
Area Under The Curve ◽  
Neurofibromatosis Type ◽  
Prediction Algorithm ◽  
In Silico Prediction ◽  
Web Based

Neurofibromatosis type 1, characterized by neurofibromas and café-au-lait macules, is one of the most common genetic disorders caused by pathogenic NF1 variants. Because of the high proportion of splicing mutations in NF1, identifying variants that alter splicing may be an essential issue for laboratories. Here, we investigated the sensitivity and specificity of SpliceAI, a recently introduced in silico splicing prediction algorithm in conjunction with other in silico tools. We evaluated 285 NF1 variants identified from 653 patients. The effect on variants on splicing alteration was confirmed by complementary DNA sequencing followed by genomic DNA sequencing. For in silico prediction of splicing effects, we used SpliceAI, MaxEntScan (MES), and Splice Site Finder-like (SSF). The sensitivity and specificity of SpliceAI were 94.5% and 94.3%, respectively, with a cut-off value of Δ Score > 0.22. The area under the curve of SpliceAI was 0.975 (p < 0.0001). Combined analysis of MES/SSF showed a sensitivity of 83.6% and specificity of 82.5%. The concordance rate between SpliceAI and MES/SSF was 84.2%. SpliceAI showed better performance for the prediction of splicing alteration for NF1 variants compared with MES/SSF. As a convenient web-based tool, SpliceAI may be helpful in clinical laboratories conducting DNA-based NF1 sequencing.

scholarly journals Cognitive phenotype in neurofibromatosis type 1

Engrami ◽  
2020 ◽  
Vol 42 (2) ◽  
pp. 69-79
Author(s):  
Jelena Todorović ◽  
Dragan Pavlović ◽  
Mirna Zelić ◽  
Lana Jerkić
Keyword(s):  
Executive Functions ◽  
Genetic Disorders ◽  
Neurofibromatosis Type ◽  
Speech Disorders ◽  
Speech Development ◽  
High Rate ◽  
Planning Problem ◽  
Preschool Period ◽  
Visuospatial Perception

Neurofibromatoses are a set of different genetic disorders that have a common characteristic of the appearance of nervous system tumors. There are three forms of the disease, of which type 1 neurofibromatosis (NF 1) is the most common. NF 1 is an inherited autosomal-dominant disease, with a high rate of new mutations. In addition to the many physical manifestations and complications that occur in persons with NF 1, there are also numerous cognitive difficulties, including lower general intellectual functioning, learning difficulties, but also problems in attention, visual abilities, executive functions, and speech. Attention disorders are up to three times more common in people with NF 1, while learning disabilities are present in more than half of these subjects. Disturbances in the field of visuospatial perception are recognisable even in the preschool period. About 80% of children with NF1 exhibit various speech and language disorders: slow early speech development, slower vocabulary enrichment, syntactic, semantic and phonological speech disorders. Disruption of executive functions will manifest itself in the areas of working memory, organisation, planning / problem solving. This will reflect as the underperformance in academic achievement. Nearly one-third of these persons have emotional and social problems.

scholarly journals Secondary Sarcomas: Biology, Presentation, and Clinical Care

2020 ◽  
pp. 463-474
Author(s):  
Vanessa Eulo ◽  
Harry Lesmana ◽  
Leona A. Doyle ◽  
Kim E. Nichols ◽  
Angela C. Hirbe
Keyword(s):  
Genetic Disorders ◽  
Clinical Care ◽  
Immunosuppressive Agents ◽  
Chemical Exposure ◽  
Neurofibromatosis Type ◽  
Li Fraumeni Syndrome ◽  
Patients With Cancer ◽  
Dicer1 Syndrome ◽  
Prompt Diagnosis

Secondary sarcomas are a subset of sarcomas that occur in patients with prior cancer diagnoses and are associated with environmental or genetic factors. Although secondary sarcomas are rare in general, there are predisposing factors that can substantially increase this risk in certain populations. Herein, we review the environmental factors with the strongest association of sarcoma risk, including chemical exposure, certain viruses, cytotoxic and immunosuppressive agents, chronic edema, and radiation exposure. Additionally, the most common genetic disorders that carry a predisposition for sarcoma development will be discussed, including hereditary retinoblastoma (RB), Li-Fraumeni syndrome (LFS), neurofibromatosis type 1 (NF1), and DICER1 syndrome. Although treatment does not generally differ for sporadic versus secondary sarcomas, awareness of the risk factors can alter therapeutic strategies to minimize risk, aid prompt diagnosis by increasing clinical suspicion, and allow for appropriate surveillance and genetic counseling for those patients with cancer predisposition syndromes.

scholarly journals A Case of Giant Posterior Mediastinal Mass: Gastrointestinal Stromal Tumor Developed in Neurofibromatosis Type 1 Patient.

2021 ◽  
Author(s):  
Volkan ASLAN ◽  
Fatih Gürler ◽  
ozan yazıcı ◽  
özlem erdem ◽  
ali çelik ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Genetic Disorders ◽  
Neurofibromatosis Type ◽  
Skin Lesions ◽  
Posterior Mediastinum ◽  
Pathological Examination ◽  
Imatinib Treatment ◽  
First Case ◽  
Posterior Mediastinal

Abstract Introduction: Gastrointestinal Stromal Tumors mostly located in the stomach and esophageal GIST is extremely rare. Various genetic disorders increase the risk of developing GIST, among these, NF-1 is the most common. A case of posterior mediastial GIST developing in the neurofibromatosis patient has not been reported yet.Case: A 48-year-old male patient is being evaluated with complaints of dyspnea and progressive dysphagia. Computed tomography detected a cystic, lobulated contour mass that was located at the posterior mediastinum and measuring 11 x 14x12 cm. The giant semisolid mass has been dissected from adjacent the vertebra, the esophagus, pericardium and inferior pulmonary vein and Histopathological examination revealed GİST. Pathological examination of skin lesions confirmed NF-1. Finally, NF-1-associated posterior mediastinal GIST was diagnosed and adjuvant imatinib treatment was initiated. Conclusion: To the best our knowledge, this patient was the first case, who diagnosed with posterior mediastinal GIST developing on the basis of NF-1.

scholarly journals Meta analysis of variant predictions in congenital adrenal hyperplasia caused by mutations in CYP21A2.

2021 ◽  
Author(s):  
Mayara Jorgens Prado ◽  
Rodrigo Ligabue-Braun ◽  
Arnaldo Zaha ◽  
Maria Lucia Rosa Rossetti ◽  
Amit V Pandey
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
In Silico ◽  
Meta Analysis ◽  
Genetic Disorders ◽  
In Silico Prediction ◽  
Adrenal Hyperplasia ◽  
Single Nucleotide Variants ◽  
Mild Phenotype ◽  
The Impact

Context: CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia cases (CAH), a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provides critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Objective: Analyze the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of the CYP21A2. Methods: SNVs of the CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of the CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. Results: SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews' correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). Conclusion: From our analysis, we identified four predictors of CYP21A2 pathogenicity with good performance. These results can be used for future analysis to infer the impact of uncharacterized SNVs' in CYP21A2.

scholarly journals RARE CAUSES OF SPONTANEOUS PNEUMOTHORAX: TWO CASE REPORTS

2021 ◽  
Vol 19 (2) ◽  
pp. 200-204
Author(s):  
V. Hadzhiminev V. Hadzhiminev
Keyword(s):  
Spontaneous Pneumothorax ◽  
Clinical Laboratory ◽  
Case Reports ◽  
Genetic Disorders ◽  
Surgical Techniques ◽  
Neurofibromatosis Type ◽  
Imaging Findings ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

Secondary spontaneous pneumothorax (SSP) may be a result of different rare diseases. In the following article are presented two interesting cases of SSP related to genetic disorders – Ehlers-Danlos syndrome (EDS) and Neurofibromatosis type 1 (NF-1). We share our clinical, laboratory and imaging findings as well as the surgical techniques we used and the postoperative complications we had. We performed a detailed literature review on this topic.

scholarly journals Small, low-grade ampullary neuroendocrine tumor presenting with metastasis and multiple synchronous tumors in a patient with neurofibromatosis type 1: a case report with literature review

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Kevin Xiao ◽  
Sharon Swierczynski ◽  
Gary Xiao
Keyword(s):  
Neuroendocrine Tumor ◽  
Neurofibromatosis Type 1 ◽  
Genetic Disorders ◽  
Intraepithelial Neoplasia ◽  
Neurofibromatosis Type ◽  
Whipple Procedure ◽  
Side Branch ◽  
Low Grade ◽  
Increased Risk

ABSTRACT Neurofibromatosis type 1 (NF1) is a tumor syndrome and one of the most common genetic disorders. Patients have an increased risk of developing neurologic and gastrointestinal (GI) neoplasms, but GI lesions are often underrecognized since most cases are asymptomatic. It is extremely rare to see multiple types of abdominal tumors synchronously in NF1. In this case, we describe a patient presenting with a small, low-grade periampullary neuroendocrine tumor (NET) that underwent endoscopic submucosal dissection and later pancreaticoduodenectomy (Whipple procedure). This led to findings of lymph node and distant metastasis of her NET, and the incidental discovery of gastrointestinal stromal tumors, extensive pancreatic intraepithelial neoplasia, and main duct and side branch intraductal pancreatic mucinous neoplasm. The synchronous presence of these lesions has not been reported in the literature.

scholarly journals Neurofibromatosis type 1 associated with coarctation of the abdominal aorta

2021 ◽  
Author(s):  
Reema Al Essa ◽  
Mohammed Al Jasser
Keyword(s):  
Abdominal Aorta ◽  
Neurofibromatosis Type 1 ◽  
Arteriovenous Malformations ◽  
Autosomal Dominant ◽  
Rare Complication ◽  
Genetic Disorders ◽  
Neurofibromatosis Type ◽  
Arterial Stenosis

Neurofibromatosis type 1 (NF1) is one of the most autosomal dominant genetic disorders. NF1 vasculopathy is a rare complication of NF1 with prevalence up to 6% including aneurysms, arterial stenosis, aorta coarctation and arteriovenous malformations [...]

scholarly journals Screening in silico predicted remotely acting NF1 gene regulatory elements for mutations in patients with neurofibromatosis type 1

2013 ◽  
Vol 7 (1) ◽  
pp. 18 ◽  
Author(s):  
Stephen E Hamby ◽  
Pablo Reviriego ◽  
David N Cooper ◽  
Meena Upadhyaya ◽  
Nadia Chuzhanova
Keyword(s):  
Neurofibromatosis Type 1 ◽  
In Silico ◽  
Neurofibromatosis Type ◽  
Regulatory Elements ◽  
Nf1 Gene ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

scholarly journals Neurofibromatosis Type 1 Presenting with Plexiform Neurofibromas in Two Patients: MRI Features

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Ahmet Mesrur Halefoglu
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Autosomal Dominant ◽  
Genetic Disorders ◽  
Neurofibromatosis Type ◽  
Plexiform Neurofibromas ◽  
Mri Features ◽  
History Of ◽  
Magnetic Resonance Imaging Mri ◽  
Distinguishing Features

Neurofibromatosis type 1 (NF1), also known as peripheral neurofibromatosis or von Recklinghausen’s disease, is one of the most common genetic disorders. It is inherited in an autosomal dominant pattern. Multiple cutaneous neurofibromas are hallmark lesions of NF1. Localized and plexiform neurofibromas of the paraspinal and sacral region are the most common abdominal neoplasms in NF1. Herein, we report two patients with a known history of NF1 presenting with multiple, extensive localized and plexiform neurofibromas. We describe the important distinguishing features of these tumors as seen on magnetic resonance imaging (MRI), including very bright signal intensity and target sign on T2 weighted images.

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