scholarly journals Comprehensive Mutation Scanning of NF1 in Apparently Sporadic Cases of Pheochromocytoma

2006 ◽  
Vol 91 (9) ◽  
pp. 3478-3481 ◽  
Author(s):  
Birke Bausch ◽  
Ann-Cathrin Koschker ◽  
Martin Fassnacht ◽  
Johanna Stoevesandt ◽  
Michael M. Hoffmann ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Susceptibility Gene ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Mutation Scanning ◽  
Lisch Nodules ◽  
Rare Manifestation ◽  
Nf1 Gene ◽  
Sporadic Cases ◽  
Sporadic Pheochromocytoma

Abstract Background: Pheochromocytoma is a rare manifestation in patients with neurofibromatosis type 1 (NF 1). The 57-exon susceptibility gene NF1 has so far not been systematically scanned for unexpected germline mutations in individuals with sporadic pheochromocytoma. Methods: Twenty-seven patients with bilateral adrenal and/or extraadrenal abdominal pheochromocytoma not carrying germline mutations of the genes VHL, RET, SDHB, and SDHD were selected from the European-American pheochromocytoma registry. All 57 exons and flanking intronic regions of the NF1 gene were PCR amplified using newly designed primer pairs to exclude the amplification of pseudogenes. Intragenic mutation scanning was performed using denaturing HPLC and bidirectional direct sequencing. Results: Of the 27 apparently sporadic cases, one (4%) was found to have a pathogenic germline NF1 mutation, Leu303Arg. Clinical reevaluation of this individual, who had bilateral pheochromocytoma, revealed classic, but very mild, features of NF 1, one cutaneous neurofibroma, axillary freckling, and Lisch nodules of the iris as well as a few café-au-lait spots. Conclusions: In the absence of germline mutations in VHL, RET, SDHD, and SDHB, patients with pheochromocytoma, especially with bilateral disease, should be checked thoroughly for clinical lesions suggestive of underlying syndromes such as the cutaneous and ophthalmological features characteristic of NF 1.

First Place—Resident Clinical Science Award 1997: Germline screening of the NF-2 gene in families with unilateral vestibular schwannoma

1998 ◽  
Vol 119 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Paul H. Bikhazi ◽  
Anil K. Lalwani ◽  
Eugene J. Kim ◽  
Nadim Bikhazi ◽  
Ali Attaie ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Type Ii ◽  
Chain Reaction ◽  
Neurofibromatosis Type Ii ◽  
Polymerase Chain ◽  
Head Neck

Vestibular schwannoma may present clinically in two forms: sporadic unilateral or hereditary bilateral. Familial transmission of vestibular schwannoma is known to occur only in neurofibromatosis type II (NF-2). We have previously described the clinical characteristics of unilateral vestibular schwannoma presenting in families, in the absence of ther criteria necessary for the diagnosis of NF-2. Polymerase chain reaction–single strand chain polymorphism was used to screen for germline NF-2 gene mutations in six families with unilateral vestibular schwannoma. Direct sequencing of DNA from blood was done in affected subjects from three families. No germline mutations were identified. Because NF-2 gene mutations are detected in only 33% of patients with NF-2, hereditary transmission of mutations cannot be entirely excluded. However, in the absence of germline mutations in the NF-2 gene, familial occurrence of unilateral vestibular schwannoma more likely represents either a chance somatic NF-2 gene mutation or originates from a separate genetic loci. (Otolaryngol Head Neck Surg 1998;119:1–6.)

scholarly journals Characterisation of germline mutations in the neurofibromatosis type 1 (NF1) gene.

1995 ◽  
Vol 32 (9) ◽  
pp. 706-710 ◽  
Author(s):  
M Upadhyaya ◽  
J Maynard ◽  
M Osborn ◽  
S M Huson ◽  
M Ponder ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Nf1 Gene

scholarly journals Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Gustavo Fernandes ◽  
Mirela Souto ◽  
Frederico Costa ◽  
Edite Oliveira ◽  
Bernardo Garicochea
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Tandem Duplication ◽  
Cancer Susceptibility ◽  
Direct Sequencing ◽  
Genetic Disorder ◽  
Clinical Signs ◽  
Neurofibromatosis Type ◽  
Genetic Alterations ◽  
Nf1 Gene

Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1) which codifies the protein neurofibromin. The frequent genetic alterations that modify neurofibromin function are deletions and insertions. Duplications are rare and phenotype in patients bearing duplication of NF1 gene is thought to be restricted to developmental abnormalities, with no reference to cancer susceptibility in these patients. We evaluated a patient who presented with few clinical signs of neurofibromatosis type 1 and a conspicuous personal and familiar history of different types of cancer, especially lymphoproliferative malignancies. The coding region of the NF-1 gene was analyzed by real-time polymerase chain reaction and direct sequencing. Multiplex ligation-dependent probe amplification was performed to detect the number of mutant copies. The NF1 gene analysis showed the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D. Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689) flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were three signals (RP5-1002G3conRP5-92689) in the interphases analyzed and two signals (RP5-1002G3conRP5-92689) in 93% of cells. These findings show a tandem duplication of 17q11.2.Conclusion. The case suggests the possibility that NF1 gene duplication may be associated with a phenotype characterized by lymphoproliferative disorders.

scholarly journals The NF1 gene: a frequent mutational target in sporadic pheochromocytomas and beyond

2013 ◽  
Vol 20 (4) ◽  
pp. C13-C17 ◽  
Author(s):  
Jenny Welander ◽  
Peter Söderkvist ◽  
Oliver Gimm
Keyword(s):  
Mrna Expression ◽  
Loss Of Heterozygosity ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Mutation Database ◽  
Nf1 Gene ◽  
Inactivating Mutations

Patients suffering from the neurofibromatosis type 1 syndrome, which is caused by germline mutations in the NF1 gene, have a tiny but not negligible risk of developing pheochromocytomas. It is, therefore, of interest that the NF1 gene has recently been revealed to carry somatic, inactivating mutations in a total of 35 (21.7%) of 161 sporadic pheochromocytomas in two independent tumor series. A majority of the tumors in both studies displayed loss of heterozygosity at the NF1 locus and a low NF1 mRNA expression. In view of previous findings that many sporadic pheochromocytomas cluster with neurofibromatosis type 1 syndrome-associated pheochromocytomas instead of forming clusters of their own, NF1 inactivation appears to be an important step in the pathogenesis of a large number of sporadic pheochromocytomas. A literature and public mutation database review has revealed that pheochromocytomas are among those human neoplasms in which somatic NF1 alterations are most frequent.

scholarly journals Severe Phenotype in Patients with Large Deletions of NF1

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2963
Author(s):  
Laurence Pacot ◽  
Dominique Vidaud ◽  
Audrey Sabbagh ◽  
Ingrid Laurendeau ◽  
Audrey Briand-Suleau ◽  
...  
Keyword(s):  
Learning Disabilities ◽  
Neurofibromatosis Type ◽  
Reference Population ◽  
Severe Phenotype ◽  
Large Deletions ◽  
Clinical Investigations ◽  
Café Au Lait Spots ◽  
Lisch Nodules ◽  
Contiguous Gene ◽  
Nf1 Gene

Complete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.

scholarly journals Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1831
Author(s):  
Camilla Russo ◽  
Carmela Russo ◽  
Daniele Cascone ◽  
Federica Mazio ◽  
Claudia Santoro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Structural Organization ◽  
Neurofibromatosis Type ◽  
Review Article ◽  
Tumor Suppressor Protein ◽  
Clinical Implications ◽  
Nf1 Gene ◽  
The Central Nervous System

Neurofibromatosis type 1 (NF1), the most frequent phakomatosis and one of the most common inherited tumor predisposition syndromes, is characterized by several manifestations that pervasively involve central and peripheral nervous system structures. The disorder is due to mutations in the NF1 gene, which encodes for the ubiquitous tumor suppressor protein neurofibromin; neurofibromin is highly expressed in neural crest derived tissues, where it plays a crucial role in regulating cell proliferation, differentiation, and structural organization. This review article aims to provide an overview on NF1 non-neoplastic manifestations of neuroradiological interest, involving both the central nervous system and spine. We also briefly review the most recent MRI functional findings in NF1.

A highly informative CA/GT repeat polymorphism in intron 38 of the human neurofibromatosis type 1 (NF1) gene

1993 ◽  
Vol 92 (4) ◽  
pp. 429-430 ◽  
Author(s):  
Conxi L�zaro ◽  
Antonia Gaona ◽  
Ganfeng Xu ◽  
Robert Weiss ◽  
Xavier Estivill
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Repeat Polymorphism ◽  
Nf1 Gene

scholarly journals Genotype-Phenotype Correlations in Neurofibromatosis Type 1: A Single-Center Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1879
Author(s):  
Marcello Scala ◽  
Irene Schiavetti ◽  
Francesca Madia ◽  
Cristina Chelleri ◽  
Gianluca Piccolo ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Copy Number Variations ◽  
Single Nucleotide Variants ◽  
Multivariate Statistical ◽  
Gene Deletions ◽  
Pathogenic Variants ◽  
Lisch Nodules ◽  
Next Generation Sequencing Ngs

Neurofibromatosis type 1 (NF1) is a proteiform genetic condition caused by pathogenic variants in NF1 and characterized by a heterogeneous phenotypic presentation. Relevant genotype–phenotype correlations have recently emerged, but only few pertinent studies are available. We retrospectively reviewed clinical, instrumental, and genetic data from a cohort of 583 individuals meeting at least 1 diagnostic National Institutes of Health (NIH) criterion for NF1. Of these, 365 subjects fulfilled ≥2 NIH criteria, including 235 pediatric patients. Genetic testing was performed through cDNA-based sequencing, Next Generation Sequencing (NGS), and Multiplex Ligation-dependent Probe Amplification (MLPA). Uni- and multivariate statistical analysis was used to investigate genotype–phenotype correlations. Among patients fulfilling ≥ 2 NIH criteria, causative single nucleotide variants (SNVs) and copy number variations (CNVs) were detected in 267/365 (73.2%) and 20/365 (5.5%) cases. Missense variants negatively correlated with neurofibromas (p = 0.005). Skeletal abnormalities were associated with whole gene deletions (p = 0.05) and frameshift variants (p = 0.006). The c.3721C>T; p.(R1241*) variant positively correlated with structural brain alterations (p = 0.031), whereas Lisch nodules (p = 0.05) and endocrinological disorders (p = 0.043) were associated with the c.6855C>A; p.(Y2285*) variant. We identified novel NF1 genotype–phenotype correlations and provided an overview of known associations, supporting their potential relevance in the implementation of patient management.

scholarly journals A Pleural Solitary Fibrous Tumor, Multiple Gastrointestinal Stromal Tumors, Moyamoya Disease, and Hyperparathyroidism in a Patient Associated with NF1

2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Yoko Yamamoto ◽  
Ken Kodama ◽  
Shigekazu Yokoyama ◽  
Masashi Takeda ◽  
Shintaro Michishita
Keyword(s):  
Moyamoya Disease ◽  
Solitary Fibrous Tumor ◽  
Gastrointestinal Stromal Tumors ◽  
Relevant Literature ◽  
Neurofibromatosis Type ◽  
Chromosome 17 ◽  
Stromal Tumors ◽  
Nf1 Gene ◽  
Multisystemic Disease ◽  
Fibrous Tumor

Neurofibromatosis type 1 (NF1), also called von Recklinghausen’s disease, is a multisystemic disease caused by an alteration of the NF1 gene, a tumor suppressor located on the long arm of chromosome 17 (17q11.2). Loss of the gene function, due to a point mutation, leads to an increase in cell proliferation and the development of several tumors. We report a 60-year-old female patient manifesting hypercalcemia due to hyperparathyroidism, a solitary fibrous tumor (SFT) of the pleura, multiple gastrointestinal stromal tumors (GISTs), and moyamoya disease associated with NF1. The SFT and GISTs were removed by staged operations. Then, hypercalcemia was successfully controlled after resection of the parathyroid adenoma. Based on a literature review, these combinations have never been reported, and the relevant literature is briefly discussed.

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