scholarly journals A Case of Persistent Foot Pain in a Neurofibromatosis Type I Patient

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Vasilis Stavrinides ◽  
Salim Nasra
Keyword(s):  
Past History ◽  
Genetic Disorder ◽  
Young Male ◽  
Neurofibromatosis Type ◽  
Chromosome 17 ◽  
Type I ◽  
Foot Pain ◽  
Loss Of Function ◽  
Increased Risk ◽  
Initial Symptoms

Introduction. This is the case of a young male patient who presented to his family physician with atypical left foot pain, which was extremely resistant to analgesia and caused significant disability. Despite extensive investigations, the cause of his pain was not identified until 18 months after his initial symptoms, when the official diagnosis of malignant peripheral nerve sheath tumour (MPNST) was made. Detailed review of the patient’s past history established the diagnosis of type I neurofibromatosis (NF-1), previously undetected.Discussion. NF-1 is an autosomal dominant genetic disorder caused by loss of function mutations of theNF1gene in chromosome 17. Patients with this condition are at increased risk for developing MPNSTs which, however, are treatable only in early stages.Conclusion. Although monitoring NF-1 patients for the development of MPNSTs is common practice, the index of clinical suspicion in patients without an established NF-1 diagnosis is low. Any atypical pain in young adults should raise the possibility of this malignancy, and this case illustrates the fact that MPNSTs can be the first manifestation of NF-1 in patients previously undiagnosed with the disease.

scholarly journals Neurofibromatosis Type I and Stromal Tumor with a Multiple Digestive Localization

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Amina Chaka ◽  
Farouk Ennaceur ◽  
Mohamed Amine Tormen ◽  
Ibtissem Korbi ◽  
Faouzi Noomen ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Stromal Tumor ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Multisystem Disorder ◽  
Cell Tissue ◽  
Increased Risk ◽  
Recklinghausen Disease ◽  
Made In

Neurofibromatosis type I (NF1) is also known as von Recklinghausen disease. It is a genetic disorder that affects the growth and development of nerve cell tissue, which is characterized by a multisystem disorder and an increased risk for cancer. The incidence of gastroduodenal stromal tumor during Recklinghausen disease can reach 35% in autopsies and 5% in clinical cases. In our case, the diagnosis of neurofibromatosis type I was made in a middle-aged women initially diagnosed with a pancreaticoduodenal tumor.

scholarly journals Characterization of Two Loss-of-Function NF1 Variants in Chinese Patients and Potential Molecular Interpretations of Phenotypes

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Zhang ◽  
Tianting Han ◽  
Zhiya Dong ◽  
Chuanyin Li ◽  
Wenli Lu
Keyword(s):  
De Novo ◽  
Malignant Tumors ◽  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Chinese Patients ◽  
Bone Lesions ◽  
Loss Of Function ◽  
Molecular Sequence ◽  
Increased Risk ◽  
Uncertain Significance

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by cafe’-au-lait spots, skinfold freckles, the formation of neurofibromas, skeletal dysplasia, vascular dysplasia, and an increased risk of malignant tumors. In this study, two Chinese NF1 children troubled with bone lesions or hypertension were reported. A de novo NF1 mutation (c.4925T > A/p.V1642E) and a maternally inherited NF1 mutation (c.4883T > A/p.L1628∗) were identified by molecular sequence. According to the ACMG/AMP guidelines, the c.4925T > A was classified as variants of uncertain significance (VOUS) while the c.4883T > A mutation was identified as likely Pathogenic. Further study found that these two NF1 mutants had lost their function to inhibit the Ras/Erk signaling and the proliferation of cells, which could interpretate some phenotypes of these two NF1 patients. We also observed these two NF1 mutants displayed decreased protein stability with increased ubiquitination levels compared with that of wild-type NF1.

scholarly journals Pulmonary hypertension associated with neurofibromatosis type 1

2018 ◽  
Vol 27 (149) ◽  
pp. 180053 ◽  
Author(s):  
Etienne-Marie Jutant ◽  
Barbara Girerd ◽  
Xavier Jaïs ◽  
Laurent Savale ◽  
Caroline O'Connell ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Neurofibromatosis Type 1 ◽  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Pulmonary Vascular Disease ◽  
Increased Risk ◽  
Parenchymal Lung Disease ◽  
Parenchymal Lung

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a frequent autosomal dominant genetic disorder with a prevalence of 1 in 3000. Pulmonary hypertension (PH) associated with NF1 (PH-NF1) is a rare but severe complication of NF1 and is classified as Group 5 PH, defined as “PH with unclear and/or multifactorial mechanisms”. A literature review in PubMed on the association between NF1 and PH identified 18 articles describing 31 cases. PH-NF1 was characterised by a female predominance, an advanced age at diagnosis, an association with parenchymal lung disease in two out of three cases and poor long-term prognosis. NF1 is generally associated with interstitial lung disease but some cases of severe PH without parenchymal lung disease suggest that there could be a specific pulmonary vascular disease. There is no data available on the efficacy of specific pulmonary arterial hypertension treatment in PH-NF1. Therefore, these patients should be evaluated in expert PH centres and referred for lung transplantation at an early stage. As these patients have an increased risk of malignancy, careful assessment of the post-transplant malignancy risk prior to listing for transplantation is necessary. Clinical trials are needed to evaluate promising treatments targeting the RAS-downstream signalling pathways.

scholarly journals Moyamoya syndrome associated with neurofibromatosis type I in a pediatric patient

2011 ◽  
Vol 129 (2) ◽  
pp. 110-112 ◽  
Author(s):  
Luiz Guilherme Darrigo Júnior ◽  
Elvis Terci Valera ◽  
André de Aboim Machado ◽  
Antonio Carlos dos Santos ◽  
Carlos Alberto Scrideli ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Moyamoya Syndrome ◽  
Radiological Findings ◽  
Convulsive Seizures ◽  
Age Range

CONTEXT: Neurofibromatosis type 1 (NF-1) is the most prevalent autosomal dominant genetic disorder among humans. Moyamoya disease is a cerebral vasculopathy that is only rarely observed in association with NF-1, particularly in the pediatric age range. The present study reports an occurrence of this association in an infant. CASE REPORT: An eight-month-old female presented convulsive seizures with clonic movements. The patient suffered an ischemic stroke with hemiparesis. Magnetic resonance imaging revealed radiological findings compatible with moyamoya disease. The diagnosis of NF-1 was made at the age of 20 months. CONCLUSION: Despite the rarity of this association in childhood, children with focal neurological symptoms and a diagnosis of NF-1 deserve to be investigated for moyamoya syndrome.

scholarly journals Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome

2016 ◽  
Vol 213 (7) ◽  
pp. 1163-1174 ◽  
Author(s):  
Marije E.C. Meuwissen ◽  
Rachel Schot ◽  
Sofija Buta ◽  
Grétel Oudesluijs ◽  
Sigrid Tinschert ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Genetic Disorders ◽  
Genetic Disorder ◽  
Congenital Infection ◽  
Infectious Agent ◽  
Negative Regulator ◽  
Type I ◽  
Loss Of Function

Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders.

scholarly journals Fanca deficiency reduces A/T transitions in somatic hypermutation and alters class switch recombination junctions in mouse B cells

2014 ◽  
Vol 211 (6) ◽  
pp. 1011-1018 ◽  
Author(s):  
Thuy Vy Nguyen ◽  
Lydia Riou ◽  
Saïd Aoufouchi ◽  
Filippo Rosselli
Keyword(s):  
B Cells ◽  
Somatic Hypermutation ◽  
Bone Marrow Failure ◽  
Genetic Disorder ◽  
Point Mutations ◽  
Class Switch Recombination ◽  
Loss Of Function ◽  
Nhej Pathway ◽  
Class Switch ◽  
Increased Risk

Fanconi anemia is a rare genetic disorder that can lead to bone marrow failure, congenital abnormalities, and increased risk for leukemia and cancer. Cells with loss-of-function mutations in the FANC pathway are characterized by chromosome fragility, altered mutability, and abnormal regulation of the nonhomologous end-joining (NHEJ) pathway. Somatic hypermutation (SHM) and immunoglobulin (Ig) class switch recombination (CSR) enable B cells to produce high-affinity antibodies of various isotypes. Both processes are initiated after the generation of dG:dU mismatches by activation-induced cytidine deaminase. Whereas SHM involves an error-prone repair process that introduces novel point mutations into the Ig gene, the mismatches generated during CSR are processed to create double-stranded breaks (DSBs) in DNA, which are then repaired by the NHEJ pathway. As several lines of evidence suggest a possible role for the FANC pathway in SHM and CSR, we analyzed both processes in B cells derived from Fanca−/− mice. Here we show that Fanca is required for the induction of transition mutations at A/T residues during SHM and that despite globally normal CSR function in splenic B cells, Fanca is required during CSR to stabilize duplexes between pairs of short microhomology regions, thereby impeding short-range recombination downstream of DSB formation.

scholarly journals Genetic analyses of the NF1 gene in Turkish neurofibromatosis type I patients and definition of three novel variants

2017 ◽  
Vol 20 (1) ◽  
pp. 13-20 ◽  
Author(s):  
SD Ulusal ◽  
H Gürkan ◽  
E Atlı ◽  
SA Özal ◽  
M Çiftdemir ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Diagnosis ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Next Generation ◽  
Loss Of Function ◽  
Pathogenic Variants ◽  
Nf1 Gene ◽  
Generation Sequencing

Abstract Neurofibromatosis Type I (NF1) is a multi systemic autosomal dominant neurocutaneous disorder predisposing patients to have benign and/or malignant lesions predominantly of the skin, nervous system and bone. Loss of function mutations or deletions of the NF1 gene is responsible for NF1 disease. Involvement of various pathogenic variants, the size of the gene and presence of pseudogenes makes it difficult to analyze. We aimed to report the results of 2 years of multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) for genetic diagnosis of NF1 applied at our genetic diagnosis center. The MLPA, semiconductor sequencing and Sanger sequencing were performed in genomic DNA samples from 24 unrelated patients and their affected family members referred to our center suspected of having NF1. In total, three novel and 12 known pathogenic variants and a whole gene deletion were determined. We suggest that next generation sequencing is a practical tool for genetic analysis of NF1. Deletion/duplication analysis with MLPA may also be helpful for patients clinically diagnosed to carry NF1 but do not have a detectable mutation in NGS.

scholarly journals Glioblastoma Multiforme in the Posterior Cranial Fossa in a Patient with Neurofibromatosis Type I

2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Marike L. D. Broekman ◽  
Roelof Risselada ◽  
JooYeon Engelen-Lee ◽  
Wim G. M. Spliet ◽  
Bon H. Verweij
Keyword(s):  
Neurofibromatosis Type ◽  
Type I ◽  
High Grade ◽  
High Grade Astrocytoma ◽  
Increased Risk ◽  
Pilocytic Astrocytomas ◽  
Benign Nature ◽  
Cranial Fossa ◽  
The Brain

Patients with Neurofibromatosis type 1 (NF1) have an increased risk of developing neoplasms. The most common brain tumors, found in 15%–20% of NF1 patients, are hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. These tumors generally have a benign nature. NF1 patients are predisposed to a 5-fold increased incidence of high-grade astrocytomas, which are usually located in supratentorial regions of the brain. We present an NF1 patient who developed a high-grade astrocytoma in the posterior fossa and discuss possible pathophysiological mechanisms.

scholarly journals Retroviral Integration at the Epi1Locus Cooperates with Nf1 Gene Loss in the Progression to Acute Myeloid Leukemia

2001 ◽  
Vol 75 (19) ◽  
pp. 9427-9434 ◽  
Author(s):  
Susan M. Blaydes ◽  
Scott C. Kogan ◽  
Bao-Tran H. Truong ◽  
Debra J. Gilbert ◽  
Nancy A. Jenkins ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Neurofibromatosis Type ◽  
Juvenile Myelomonocytic Leukemia ◽  
Loss Of Function ◽  
Hematopoietic Stem ◽  
Retroviral Integration ◽  
Increased Risk ◽  
Nf1 Gene ◽  
Acute Myeloid

ABSTRACT Juvenile myelomonocytic leukemia (JMML) is a disease that occurs in young children and is associated with a high mortality rate. In most patients, JMML has a progressive course leading to death by virtue of infection, bleeding, or progression to acute myeloid leukemia (AML). As it is known that children with neurofibromatosis type 1 syndrome have a markedly increased risk of developing JMML, we have previously developed a mouse model of JMML through reconstitution of lethally irradiated mice with hematopoietic stem cells homozygous for a loss-of-function mutation in the Nf1 gene (D. L. Largaespada, C. I. Brannan, N. A. Jenkins, and N. G. Copeland, Nat. Genet. 12:137–143, 1996). In the course of these experiments, we found that all these genetically identical reconstituted mice developed a JMML-like disorder, but only a subset went on to develop more acute disease. This result strongly suggests that additional genetic lesions are responsible for disease progression to AML. Here, we describe the production of a unique tumor panel, created using the BXH-2 genetic background, for identification of these additional genetic lesions. Using this tumor panel, we have identified a locus, Epi1, which maps 30 to 40 kb downstream of theMyb gene and appears to be the most common site of somatic viral integration in BXH-2 mice. Our findings suggest that proviral integrations at Epi1 cooperate with loss of Nf1to cause AML.

scholarly journals Neurofibromatosis Type I (Von Recklinghausen Disease): A Case Report and Review of the Literature

2020 ◽  
Vol 47 (2) ◽  
pp. 43-46
Author(s):  
J. Pozharashka ◽  
L. Dourmishev ◽  
E. Bardarov ◽  
M. Balabanova ◽  
L. Miteva
Keyword(s):  
Genetic Disorder ◽  
Surgical Excision ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Multiple Organs ◽  
Laboratory Investigations ◽  
Von Recklinghausen ◽  
Typical Skin

AbstractNeurofibromatosis type I is an autosomal dominant genetic disorder with an incidence of about 1 in 3000 births. Apart from the typical skin involvement NF1 may affect multiple organs with ocular, neurological, skeletal and cardiovascular manifestations. We present a case of a 38-year-old man with multiple café-au-lait macules and hundreds of neurofibromas disseminated on the trunk and extremities dating from childhood. To establish the diagnosis and to exclude any complications we performed multiple examinations, including skin biopsy, laboratory investigations, ophthalmologic assessment, consultations with a neurologist, internist and orthopedist, etc. The treatment of cutaneous NF1 is mainly symptomatic. Surgical excision aims to achieve cosmetic results. Recently novel and perspective conservative therapies have been investigated. In order to ensure better outcome for the patients with NF1 long-term multi-disciplinary approach is advised.

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