BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 ...BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 patients.In NF1-associated GIST,KIT and PDGFRA mutations are frequently absent and imatinib is ineffective.Surgical resection is first-line treatment.CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass.Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head,face,trunk,and limbs.Her abdomen was soft and nontender.No masses were palpated.Digital rectal examination was unremarkable.Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor.Laparoscopy was performed,which identified eight well-demarcated masses in the jejunum.All were resected and pathologically diagnosed as GISTs.The patient was discharged on day 7 after surgery without complications.No tumor recurrence was evident at the 6-mo follow-up.CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.展开更多
AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detect...AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detecting the suspicious pathogenic variant type,the pathogenic variant sites of the patient and the patient’s family members were verified by multiple ligation dependent probe amplification and Sanger sequencing.Sift,polyphen-2,Mutation Taster and GERP++software were used to predict the pathogenicity of the unknown loci.The clinical data,diagnosis and treatment process of the patients were reviewed.Using the keyword“NF1;frameshift pathogenic variant”,relevant literature was gathered for analysis from Chinese and international databases,with articles dating from the establishment of each database to April 2022.RESULTS:A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient.The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497.Sanger sequencing validation and segregation analysis were performed,which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family.This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA(p.I1497Nfs*12).Relevant literature retrieval found 7 Chinese articles and 12 foreign articles.With NF1 gene mutation,mutation types are diverse,including point mutation,frameshift mutation,splice site mutation,exon mutation,chimeric mutation and de novo mutation.Foreign reports are based on autosomal dominant inheritance.CONCLUSION:This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family,expanding the mutational spectrum of the NF1 gene.展开更多
Background:To investigate the common symptoms after Covid-19 infection,characteristics of adverse events after vaccination,changes in clinical manifestations related to Neurofibromatosis type 1(NF1),as well as the cur...Background:To investigate the common symptoms after Covid-19 infection,characteristics of adverse events after vaccination,changes in clinical manifestations related to Neurofibromatosis type 1(NF1),as well as the current vaccination status and factors related to vaccine hesitation among NF1 patients,in order to provide a basis for scientific protection and vaccine acceptance in NF1 individuals in the new phase of pandemic management.Methods:From December 29,2022,to January 10,2023,we conducted a self-assessment questionnaire survey among diagnosed NF1 patients.General data were provided including sex,age,main clinical presentations,and current treatment.This study mainly focused on the infection and vaccination status of Covid-19 among these patients with NF1.The data were statistically analyzed using SPSS26.0 software.Results:Of the 250 questionnaires distributed,226 were valid.Among the 164 patients(72.6%)with Covid-19 infection,the most common infection symptoms and incidence of patients were not significantly different from those in the normal population(P>0.05),but the incidence of symptoms such as nasal congestion,headache,myalgia,sore throat,abdominal pain,diarrhea,and eye discomfort was higher than that in the normal population(P<0.05),and no severe infection was observed;186 patients(82.3%)had completed the Covid-19 vaccination,and more than half of those who were not vaccinated had no plans for vaccination.Among the vaccinated patients,there was no significant difference in the incidence of adverse events,such as fever,pain,redness,and swelling at the injection site after vaccination,compared to the normal population(P>0.05),but the incidence of fatigue and headache was higher in NF1 patients(P<0.001).Most patients with NF1 believe that there is no significant progressive change in NF1-related clinical manifestations after Covid-19 infection and vaccination.Conclusion:Currently,some NF1 patients appear to be worried about the evolution of their disease after Covid-19 infection in the face of large fluctuations in the pandemic situation,and some patients hesitate to receive the vaccine due to their special disease condition.Thus,clinical trials should be conducted to develop a refined pandemic response and vaccination program for this special group.展开更多
We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1(NF1). Three members of this family were NF1 patients presenting with different clinical phenotypes and the ot...We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1(NF1). Three members of this family were NF1 patients presenting with different clinical phenotypes and the others were asymptomatic. Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared with a reference database. One novel NF1 frame-shift mutation c.703_704delTA, which resulted in a premature stop signal at codon 720 and the synthesis of truncated, was revealed. This mutation segregated with the NF1 members is likely responsible for the pathogenesis of NF1 in the family.展开更多
Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofi...Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofibromin is down-regulating the biological activity of the proto-oncoprotein Ras by acting as a Ras-specific GTPase activating protein. In this study, we identified a Chinese family affected with neurofibromatosis type 1. The known gene NF1 associated with NF1 was studied by linkage analysis and by direct sequencing of the entire coding region and exon-intron boundaries of the NF1 gene. The R1947X mutation of NF1 was identified, which was co-segregated with affected individuals in the Chinese family, but not present in unaffected family members. This is the first report, which states that the R1947X mutation of NF1 may be one of reasons for neurofibromatosis type 1 in Chinese population.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of ...BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.展开更多
Neurofibromatosis is a dominantly inheriteddefect of the ectoderm,characterized by cafe au laitspots since the childhood and multiple tumorsderived from elements of peripheral and cranialnerves.Hernia-like tumors of v...Neurofibromatosis is a dominantly inheriteddefect of the ectoderm,characterized by cafe au laitspots since the childhood and multiple tumorsderived from elements of peripheral and cranialnerves.Hernia-like tumors of various sizes can oftenbe felt under the skin and serve as a valuablecharacteristic in making diagnosis.However,theycan also affect brain,vegetative nerve system or othertissues and lead to bony abnormalities,mentaldisturbances and sometimes,endocrine abnormalities,展开更多
BACKGROUND Neurofibromatosis type 1(NF1)is an inherited autosomal dominant disorder affecting many parts of the body with caféau lait spots,skeletal deformity,and scoliosis.A familial case of NF1 with scoliosis a...BACKGROUND Neurofibromatosis type 1(NF1)is an inherited autosomal dominant disorder affecting many parts of the body with caféau lait spots,skeletal deformity,and scoliosis.A familial case of NF1 with scoliosis and a painless mass had not yet been reported.CASE SUMMARY We describe the case of a 15-year-old male patient with a painless lump on the left side of his neck for 10 years and scoliosis.His right shoulder was about 5 cm lower than the left,the left side of his face was deformed,and the left submandibular skin was relaxed.The folding and drooping were obvious and movement was poor.Computed tomography revealed the involvement of the neck,upper chest wall,and surrounding left shoulder,accompanied by bone changes and scoliosis.Histological evaluation showed subepidermal pale blue mucoid degeneration,fibrous fusiform cells in the dermis in a fascicular,woven arrangement.His mother had the same medical history.The diagnosis was neurofibromatosis of the left neck.Various parts of the tumor tissue were serially resected during several visits.Eight months after surgery,there was a slight tendency to regrow.CONCLUSION This case of slow-progressing NF1 highlights the importance of early diagnosis and treatment to reduce its impact on the patient’s growth and development.展开更多
AIM:To examine neuroretinal function by using the multifocal electroretinography(mf ERG)test in patients with neurofibromatosis type 1(NF1)without optic pathway gliomas(OPGs).METHODS:This study was conducted on 35 pat...AIM:To examine neuroretinal function by using the multifocal electroretinography(mf ERG)test in patients with neurofibromatosis type 1(NF1)without optic pathway gliomas(OPGs).METHODS:This study was conducted on 35 patients(35 eyes)with NF1 and 30 healthy subjects(30 eyes)for the control group.Each subject underwent a complete ophthalmological examination including spectral domainoptical coherence tomography(SD-OCT)and mf ERG.The 1.5-Tesla magnetic resonance imaging(MRI)scan of the brain was performed in NF1 patients to assess the presence of OPGs.All participants were recruited having a best corrected visual acuity(BCVA)of no less than 20/20 in each eye.The amplitude and implicit time of the P1 wave(first-order Kernel component)were evaluated on mf ERG.Data analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual field.RESULTS:Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy controls,while the reduction was not significant in the 2 central degrees between the groups.A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group,with lower amplitudes detected in the nasal quadrants.No differences in the implicit times were recorded in the 2 central degrees and in the 4 quadrants as compared between NF1 patients and controls.CONCLUSION:Impaired neuroretinal function in NF1 patients is expressed in a decreased amplitude of the P1-wave between 2 and 25 central retinal degrees on mf ERG.Altered intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate(c AMP)generation,can be involved.The possible use of mf ERG as subclinical retinal damage indicator has a potential utility in clinical practice for the follow-up of NF1 patients.展开更多
Dear Editor,I am Satoru Kase,from the Department of Ophthalmology,Faculty of Medicine and Graduate School of Medicine,Hokkaido University,Sapporo City,Japan.I write to present a case of neurofibromatosis type 1(NF1)...Dear Editor,I am Satoru Kase,from the Department of Ophthalmology,Faculty of Medicine and Graduate School of Medicine,Hokkaido University,Sapporo City,Japan.I write to present a case of neurofibromatosis type 1(NF1)showing massive hemorrhage during involutional blepharoptosis surgery.展开更多
BACKGROUND Neurofibromatosis type 1(NF-1)is a common autosomal dominant genetic disorder.It is characterized by café-au-lait spots and cutaneous neurofibromas.Although NF-1 typically involves the skin,nerves,bone...BACKGROUND Neurofibromatosis type 1(NF-1)is a common autosomal dominant genetic disorder.It is characterized by café-au-lait spots and cutaneous neurofibromas.Although NF-1 typically involves the skin,nerves,bones,and eyes,vascular manifestation in the form of devastating hemorrhage can occur rarely.CASE SUMMARY We present the case of a 47-year-old female with NF-1 who had a ruptured right lower limb arterial malformation.She presented with sudden right lower limb swelling for two hours and symptoms of hemorrhagic shock on admission.The physical examination revealed a right lower limb presenting as elephantiasis and visible dark-brown pigmentation over a large area.Computed tomography angiography showed right lower limb arteriovenous malformation.Therefore,the patient underwent emergency right lower limb digital subtraction angiography(DSA)and vascular embolization after blood transfusions.However,after DSA,vascular embolization,and repeated blood transfusions,the anemia and right lower limb swelling and tenderness did not improve.As a result,the patient underwent right lower extremity above-knee amputation.After amputation,the patient's hemoglobin level improved significantly without blood transfusion,and she was discharged from the hospital after the incision healed.Postoperative pathological examination suggested neurogenic tumors.No other complications had occurred 1-year follow-up.CONCLUSION Vascular malformation and rupture are fatal complications of NF-1.Embolization may not provide complete relief,the patient might need to undergo neurofibroma resection or amputation.展开更多
BACKGROUND Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components.They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1.Isolated colonic ...BACKGROUND Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components.They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1.Isolated colonic neurofibroma without systemic manifestations is a rarely reported clinical entity.Here we present a case of a 51 years old male with an isolated colonic neurofibroma seen on a screening colonoscopy.CASE SUMMARY Fifty-one years old male who was otherwise healthy without a significant family history of cancer underwent a screening colonoscopy and was found have a 2.3 cm×1.4 cm lesion in the colon.Tissue biopsy revealed a spindle cell tumor.Magnetic resonance imaging of the pelvis was negative for adenopathy.He underwent an endoscopic ultrasound that showed an ill-defined avascular lesion of mixed echogenicity measuring 2.8 cm×15.2 cm in the submucosa with no communication with muscularis mucosa or propria.Immunohistochemistry staining of the tumor was strongly positive for S100,with rare penetrating axons deep within the tumor.Tumor cells were negative for c-kit and desmin and had low Ki-67 index.These findings were consistent with a solitary colonic submucosal neurofibroma.A detailed history and physical examination did not reveal any evidence of extraintestinal neurofibromatosis.He underwent transanal surgical resection of the tumor.The patient tolerated the procedure well without any complications.CONCLUSION While neurofibromas have been well described in literature,an isolated colonic neurofibroma is a rare pathological entity.Malignant transformation of neurofibromas has been reported in patients with neurofibromatosis syndromes.We report a case of isolated colonic neurofibroma and highlight the importance of resection due to the increased risk of tumorigenesis.展开更多
Dear editor,I am Dr.Jie Peng,from the Department of Ophthalmology,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China.I write to present a case report of a novel in-frame del...Dear editor,I am Dr.Jie Peng,from the Department of Ophthalmology,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China.I write to present a case report of a novel in-frame deletion mutation c.17779del TAC of neurofibromatosis type 1 in a Chinese boy with bilateral blindness.Neurofibromatosis type 1(NF1;OMIM#162200),an autosomal dominant disease,is caused by mutations in the NF1gene.The incidence of this disease is around 1 in 3500展开更多
We report in this series 5 cases of neurofibromatosis type 1 (NF1). The mean age of the patients was 14.8 years (±9.65) with extremes ranging from 3 to 27 years. Three patients were female (60%) and two were male...We report in this series 5 cases of neurofibromatosis type 1 (NF1). The mean age of the patients was 14.8 years (±9.65) with extremes ranging from 3 to 27 years. Three patients were female (60%) and two were male (40%). Three of our patients (60%) had no history of NF1 and two were monophthalmic because of plexiform neurofibromas involving the eyelid. Both cutaneous and plexiform neurofibromas were found in all our patients. The latter were of variable location: one on the chin, two on the left temporofacial region and two on the left upper eyelid. They were the cause of complications such as blindness in two patients. Café au lait macule (CALMs) was also present in all our patients. No cases of optic nerve glioma were found in the 3 patients (60%) who underwent an orbitocerebral CT scan. Lish nodules were observed in 4 patients (80%). With the exception of the 3-year-old female patient who was not old enough to go to school, all the other four patients dropped out of school because of the stigma attached to them.展开更多
Neurofibromatosis type 1 (NF-1) is a common genetic disorder with a highly variable phenotype. The disease affects both proliferation and differentiation of cells of neurectodermal origin. The presence of tumors is ve...Neurofibromatosis type 1 (NF-1) is a common genetic disorder with a highly variable phenotype. The disease affects both proliferation and differentiation of cells of neurectodermal origin. The presence of tumors is very common like benign nodular neurofibromas. Tumors with unclear prognosis may be present like plexiform neurofibromas whose prognosis is more uncertain. While many organs exhibit pathologies, most commonly affected are the nervous system, skin, gastrointestinal tract and heart. Oral abnormalities are also very common: 72% of NF-1 patients exhibit pathologies in oral mucosa, gums, maxillary and temporomandibular joints, and teeth. The incidence of NF-1 and its relationship to the prevalence of caries have been discussed in other researches. It is known that poor oral hygiene plays a key role in the development of periodontal disease and caries. Here we review the oral manifestations of neurofibromatosis type 1 that we illustrate by a patient followed in the center of rare diseases of the hospital Henri Mondor, clinical service in which we work.展开更多
Background Neurofibromatosis type 1(NF1)is an autosomal dominant inherited disorder.It can affect multiple systems of the body and cause severe disfigurement and discomfort in these patients.There are two types of neu...Background Neurofibromatosis type 1(NF1)is an autosomal dominant inherited disorder.It can affect multiple systems of the body and cause severe disfigurement and discomfort in these patients.There are two types of neurofibromas,named cutaneous and plexiform neurofibromas.The latter type may transform into malignant peripheral nerve sheath tumors(MPNSTs).Surgical resection is difficult to perform owing to the complex tissue structure of neurofibromas;therefore,it is necessary to develop novel and effective therapies for the treatment of these tumors.Programmed cell death protein 1(PD-1)/programmed cell death-ligand 1(PD-L1)-related immune checkpoint inhibitors have been proven effective for various cancers,and the positive expression of PD-L1 and tumor-infiltrating lymphocytes(TILs)has been recognized as a biomarker for the response to immune checkpoint therapy.Methods We conducted immunohistochemistry(IHC)staining to detect PD-L1 expression in plexiform neurofibroma and MPNST tissue samples.Reverse transcription-polymerase chain reaction(RT-PCR)and western blotting were performed to detect PD-L1 and PD-1 expression in MPNST cell lines.IHC staining was used to show immune cell infiltration in NF1 and MPNST tissues.Results IHC staining showed PD-L1 positive expression in neurofibromas and MPNST tumor tissues.In addition,qPCR and western blotting showed high expression of PD-L1 in MPNST tumor cells.IHC staining revealed that aberrant T lymphocytes infiltrated the plexiform neurofibroma and MPNST tumor tissues.Conclusion These results indicate that immune checkpoint mechanisms may play a pivotal role in the development of NF1-related tumors,and immune checkpoint inhibitors may be effective for managing neurofibromas and MPNSTs.Combined therapy with other molecular agents may be explored in the future.展开更多
The objectives of this study were to assess the safety and efficacy of intralesionally administered diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This was a proof-of-concept, prospective...The objectives of this study were to assess the safety and efficacy of intralesionally administered diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This was a proof-of-concept, prospective, safety and efficacy study of the effect of intralesionally administered diclofenac 25 mg/ml given once a week to 3 target cutaneous neurofibromas for 4 consecutive weeks. Overall, there was no significant change in neurofibroma size. During the study, some treated lesions developed signs of necrosis and fell off after a few weeks, but none of the control neurofibromas fell off. There were no significant changes in patient’s vital signs. A few adverse events occurred, mostly at the injection sites. During the study, some neurofibromas developed necrosis after the diclofenac injections and eventually detached from the patient. Overall, diclofenac was well tolerated, suggesting minimal systemic exposure, which required confirmation and further studies, including bioavailability analysis.展开更多
基金Supported by Clinical Research Fund Project of Zhejiang Medical Association,China,No.2021ZYC-A173.
文摘BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 patients.In NF1-associated GIST,KIT and PDGFRA mutations are frequently absent and imatinib is ineffective.Surgical resection is first-line treatment.CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass.Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head,face,trunk,and limbs.Her abdomen was soft and nontender.No masses were palpated.Digital rectal examination was unremarkable.Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor.Laparoscopy was performed,which identified eight well-demarcated masses in the jejunum.All were resected and pathologically diagnosed as GISTs.The patient was discharged on day 7 after surgery without complications.No tumor recurrence was evident at the 6-mo follow-up.CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.
基金Supported by National High Level Hospital Clinical Research Funding(No.2022-PUMCH-A-031)。
文摘AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detecting the suspicious pathogenic variant type,the pathogenic variant sites of the patient and the patient’s family members were verified by multiple ligation dependent probe amplification and Sanger sequencing.Sift,polyphen-2,Mutation Taster and GERP++software were used to predict the pathogenicity of the unknown loci.The clinical data,diagnosis and treatment process of the patients were reviewed.Using the keyword“NF1;frameshift pathogenic variant”,relevant literature was gathered for analysis from Chinese and international databases,with articles dating from the establishment of each database to April 2022.RESULTS:A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient.The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497.Sanger sequencing validation and segregation analysis were performed,which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family.This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA(p.I1497Nfs*12).Relevant literature retrieval found 7 Chinese articles and 12 foreign articles.With NF1 gene mutation,mutation types are diverse,including point mutation,frameshift mutation,splice site mutation,exon mutation,chimeric mutation and de novo mutation.Foreign reports are based on autosomal dominant inheritance.CONCLUSION:This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family,expanding the mutational spectrum of the NF1 gene.
基金supported by the National Natural Science Foundation of China (grant nos. 82102344 and 82172228)Shanghai Rising Star Program supported by Science and Technology Commission of Shanghai Municipality (grant no. 20QA1405600)+4 种基金Science and Technology Commission of Shanghai Municipality (grant no. 19JC1413)Natural Science Foundation of Shanghai (grant no. 22ZR1422300)“Chenguang Program” supported by Shanghai Education Development Foundation (grant no. 19CG18)Shanghai Municipal Key Clinical Specialty (grant no.shslczdzk00901)Innovative Research Team of High-level Local Universities in Shanghai (grant no. SSMUZDCX20180700)
文摘Background:To investigate the common symptoms after Covid-19 infection,characteristics of adverse events after vaccination,changes in clinical manifestations related to Neurofibromatosis type 1(NF1),as well as the current vaccination status and factors related to vaccine hesitation among NF1 patients,in order to provide a basis for scientific protection and vaccine acceptance in NF1 individuals in the new phase of pandemic management.Methods:From December 29,2022,to January 10,2023,we conducted a self-assessment questionnaire survey among diagnosed NF1 patients.General data were provided including sex,age,main clinical presentations,and current treatment.This study mainly focused on the infection and vaccination status of Covid-19 among these patients with NF1.The data were statistically analyzed using SPSS26.0 software.Results:Of the 250 questionnaires distributed,226 were valid.Among the 164 patients(72.6%)with Covid-19 infection,the most common infection symptoms and incidence of patients were not significantly different from those in the normal population(P>0.05),but the incidence of symptoms such as nasal congestion,headache,myalgia,sore throat,abdominal pain,diarrhea,and eye discomfort was higher than that in the normal population(P<0.05),and no severe infection was observed;186 patients(82.3%)had completed the Covid-19 vaccination,and more than half of those who were not vaccinated had no plans for vaccination.Among the vaccinated patients,there was no significant difference in the incidence of adverse events,such as fever,pain,redness,and swelling at the injection site after vaccination,compared to the normal population(P>0.05),but the incidence of fatigue and headache was higher in NF1 patients(P<0.001).Most patients with NF1 believe that there is no significant progressive change in NF1-related clinical manifestations after Covid-19 infection and vaccination.Conclusion:Currently,some NF1 patients appear to be worried about the evolution of their disease after Covid-19 infection in the face of large fluctuations in the pandemic situation,and some patients hesitate to receive the vaccine due to their special disease condition.Thus,clinical trials should be conducted to develop a refined pandemic response and vaccination program for this special group.
基金Supported by the National Major Scientific Equipment Program(No.2012YQ12008005)
文摘We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1(NF1). Three members of this family were NF1 patients presenting with different clinical phenotypes and the others were asymptomatic. Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared with a reference database. One novel NF1 frame-shift mutation c.703_704delTA, which resulted in a premature stop signal at codon 720 and the synthesis of truncated, was revealed. This mutation segregated with the NF1 members is likely responsible for the pathogenesis of NF1 in the family.
基金This work was supported by the National Natural Science Foundation of China(No.30571677)the National Basic Research Program of China(973 Program)(No.2007CB512000).
文摘Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofibromin is down-regulating the biological activity of the proto-oncoprotein Ras by acting as a Ras-specific GTPase activating protein. In this study, we identified a Chinese family affected with neurofibromatosis type 1. The known gene NF1 associated with NF1 was studied by linkage analysis and by direct sequencing of the entire coding region and exon-intron boundaries of the NF1 gene. The R1947X mutation of NF1 was identified, which was co-segregated with affected individuals in the Chinese family, but not present in unaffected family members. This is the first report, which states that the R1947X mutation of NF1 may be one of reasons for neurofibromatosis type 1 in Chinese population.
基金Supported by National Natural Science Foundation of China,No.81601692Program of Liaoning Province Department of Education,No.LK2016002
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.
文摘Neurofibromatosis is a dominantly inheriteddefect of the ectoderm,characterized by cafe au laitspots since the childhood and multiple tumorsderived from elements of peripheral and cranialnerves.Hernia-like tumors of various sizes can oftenbe felt under the skin and serve as a valuablecharacteristic in making diagnosis.However,theycan also affect brain,vegetative nerve system or othertissues and lead to bony abnormalities,mentaldisturbances and sometimes,endocrine abnormalities,
基金the National Natural Science Foundation of Guangdong,No.2019A1515011911the Guangdong Province High-level Clinical Key Specialist,No.SZGSP008.
文摘BACKGROUND Neurofibromatosis type 1(NF1)is an inherited autosomal dominant disorder affecting many parts of the body with caféau lait spots,skeletal deformity,and scoliosis.A familial case of NF1 with scoliosis and a painless mass had not yet been reported.CASE SUMMARY We describe the case of a 15-year-old male patient with a painless lump on the left side of his neck for 10 years and scoliosis.His right shoulder was about 5 cm lower than the left,the left side of his face was deformed,and the left submandibular skin was relaxed.The folding and drooping were obvious and movement was poor.Computed tomography revealed the involvement of the neck,upper chest wall,and surrounding left shoulder,accompanied by bone changes and scoliosis.Histological evaluation showed subepidermal pale blue mucoid degeneration,fibrous fusiform cells in the dermis in a fascicular,woven arrangement.His mother had the same medical history.The diagnosis was neurofibromatosis of the left neck.Various parts of the tumor tissue were serially resected during several visits.Eight months after surgery,there was a slight tendency to regrow.CONCLUSION This case of slow-progressing NF1 highlights the importance of early diagnosis and treatment to reduce its impact on the patient’s growth and development.
文摘AIM:To examine neuroretinal function by using the multifocal electroretinography(mf ERG)test in patients with neurofibromatosis type 1(NF1)without optic pathway gliomas(OPGs).METHODS:This study was conducted on 35 patients(35 eyes)with NF1 and 30 healthy subjects(30 eyes)for the control group.Each subject underwent a complete ophthalmological examination including spectral domainoptical coherence tomography(SD-OCT)and mf ERG.The 1.5-Tesla magnetic resonance imaging(MRI)scan of the brain was performed in NF1 patients to assess the presence of OPGs.All participants were recruited having a best corrected visual acuity(BCVA)of no less than 20/20 in each eye.The amplitude and implicit time of the P1 wave(first-order Kernel component)were evaluated on mf ERG.Data analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual field.RESULTS:Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy controls,while the reduction was not significant in the 2 central degrees between the groups.A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group,with lower amplitudes detected in the nasal quadrants.No differences in the implicit times were recorded in the 2 central degrees and in the 4 quadrants as compared between NF1 patients and controls.CONCLUSION:Impaired neuroretinal function in NF1 patients is expressed in a decreased amplitude of the P1-wave between 2 and 25 central retinal degrees on mf ERG.Altered intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate(c AMP)generation,can be involved.The possible use of mf ERG as subclinical retinal damage indicator has a potential utility in clinical practice for the follow-up of NF1 patients.
文摘Dear Editor,I am Satoru Kase,from the Department of Ophthalmology,Faculty of Medicine and Graduate School of Medicine,Hokkaido University,Sapporo City,Japan.I write to present a case of neurofibromatosis type 1(NF1)showing massive hemorrhage during involutional blepharoptosis surgery.
文摘BACKGROUND Neurofibromatosis type 1(NF-1)is a common autosomal dominant genetic disorder.It is characterized by café-au-lait spots and cutaneous neurofibromas.Although NF-1 typically involves the skin,nerves,bones,and eyes,vascular manifestation in the form of devastating hemorrhage can occur rarely.CASE SUMMARY We present the case of a 47-year-old female with NF-1 who had a ruptured right lower limb arterial malformation.She presented with sudden right lower limb swelling for two hours and symptoms of hemorrhagic shock on admission.The physical examination revealed a right lower limb presenting as elephantiasis and visible dark-brown pigmentation over a large area.Computed tomography angiography showed right lower limb arteriovenous malformation.Therefore,the patient underwent emergency right lower limb digital subtraction angiography(DSA)and vascular embolization after blood transfusions.However,after DSA,vascular embolization,and repeated blood transfusions,the anemia and right lower limb swelling and tenderness did not improve.As a result,the patient underwent right lower extremity above-knee amputation.After amputation,the patient's hemoglobin level improved significantly without blood transfusion,and she was discharged from the hospital after the incision healed.Postoperative pathological examination suggested neurogenic tumors.No other complications had occurred 1-year follow-up.CONCLUSION Vascular malformation and rupture are fatal complications of NF-1.Embolization may not provide complete relief,the patient might need to undergo neurofibroma resection or amputation.
文摘BACKGROUND Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components.They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1.Isolated colonic neurofibroma without systemic manifestations is a rarely reported clinical entity.Here we present a case of a 51 years old male with an isolated colonic neurofibroma seen on a screening colonoscopy.CASE SUMMARY Fifty-one years old male who was otherwise healthy without a significant family history of cancer underwent a screening colonoscopy and was found have a 2.3 cm×1.4 cm lesion in the colon.Tissue biopsy revealed a spindle cell tumor.Magnetic resonance imaging of the pelvis was negative for adenopathy.He underwent an endoscopic ultrasound that showed an ill-defined avascular lesion of mixed echogenicity measuring 2.8 cm×15.2 cm in the submucosa with no communication with muscularis mucosa or propria.Immunohistochemistry staining of the tumor was strongly positive for S100,with rare penetrating axons deep within the tumor.Tumor cells were negative for c-kit and desmin and had low Ki-67 index.These findings were consistent with a solitary colonic submucosal neurofibroma.A detailed history and physical examination did not reveal any evidence of extraintestinal neurofibromatosis.He underwent transanal surgical resection of the tumor.The patient tolerated the procedure well without any complications.CONCLUSION While neurofibromas have been well described in literature,an isolated colonic neurofibroma is a rare pathological entity.Malignant transformation of neurofibromas has been reported in patients with neurofibromatosis syndromes.We report a case of isolated colonic neurofibroma and highlight the importance of resection due to the increased risk of tumorigenesis.
文摘Dear editor,I am Dr.Jie Peng,from the Department of Ophthalmology,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China.I write to present a case report of a novel in-frame deletion mutation c.17779del TAC of neurofibromatosis type 1 in a Chinese boy with bilateral blindness.Neurofibromatosis type 1(NF1;OMIM#162200),an autosomal dominant disease,is caused by mutations in the NF1gene.The incidence of this disease is around 1 in 3500
文摘We report in this series 5 cases of neurofibromatosis type 1 (NF1). The mean age of the patients was 14.8 years (±9.65) with extremes ranging from 3 to 27 years. Three patients were female (60%) and two were male (40%). Three of our patients (60%) had no history of NF1 and two were monophthalmic because of plexiform neurofibromas involving the eyelid. Both cutaneous and plexiform neurofibromas were found in all our patients. The latter were of variable location: one on the chin, two on the left temporofacial region and two on the left upper eyelid. They were the cause of complications such as blindness in two patients. Café au lait macule (CALMs) was also present in all our patients. No cases of optic nerve glioma were found in the 3 patients (60%) who underwent an orbitocerebral CT scan. Lish nodules were observed in 4 patients (80%). With the exception of the 3-year-old female patient who was not old enough to go to school, all the other four patients dropped out of school because of the stigma attached to them.
文摘Neurofibromatosis type 1 (NF-1) is a common genetic disorder with a highly variable phenotype. The disease affects both proliferation and differentiation of cells of neurectodermal origin. The presence of tumors is very common like benign nodular neurofibromas. Tumors with unclear prognosis may be present like plexiform neurofibromas whose prognosis is more uncertain. While many organs exhibit pathologies, most commonly affected are the nervous system, skin, gastrointestinal tract and heart. Oral abnormalities are also very common: 72% of NF-1 patients exhibit pathologies in oral mucosa, gums, maxillary and temporomandibular joints, and teeth. The incidence of NF-1 and its relationship to the prevalence of caries have been discussed in other researches. It is known that poor oral hygiene plays a key role in the development of periodontal disease and caries. Here we review the oral manifestations of neurofibromatosis type 1 that we illustrate by a patient followed in the center of rare diseases of the hospital Henri Mondor, clinical service in which we work.
基金This work was supported by the grants from the Youth Doctor Collaborative Innovation Team Project(QC201803)of Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine,Shanghai Youth Top-Notch Talent Program(201809004)“Chenguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(19CG18)+3 种基金Science and Technology Commission of Shanghai Municipality(19JC1413)Shanghai Rising Star Program(20QA1405600)Innovative research team of high-level local universities in Shanghai(SSMU-ZDCX20180700)Shanghai Municipal Key Clinical Specialty(shslczdzk00901).
文摘Background Neurofibromatosis type 1(NF1)is an autosomal dominant inherited disorder.It can affect multiple systems of the body and cause severe disfigurement and discomfort in these patients.There are two types of neurofibromas,named cutaneous and plexiform neurofibromas.The latter type may transform into malignant peripheral nerve sheath tumors(MPNSTs).Surgical resection is difficult to perform owing to the complex tissue structure of neurofibromas;therefore,it is necessary to develop novel and effective therapies for the treatment of these tumors.Programmed cell death protein 1(PD-1)/programmed cell death-ligand 1(PD-L1)-related immune checkpoint inhibitors have been proven effective for various cancers,and the positive expression of PD-L1 and tumor-infiltrating lymphocytes(TILs)has been recognized as a biomarker for the response to immune checkpoint therapy.Methods We conducted immunohistochemistry(IHC)staining to detect PD-L1 expression in plexiform neurofibroma and MPNST tissue samples.Reverse transcription-polymerase chain reaction(RT-PCR)and western blotting were performed to detect PD-L1 and PD-1 expression in MPNST cell lines.IHC staining was used to show immune cell infiltration in NF1 and MPNST tissues.Results IHC staining showed PD-L1 positive expression in neurofibromas and MPNST tumor tissues.In addition,qPCR and western blotting showed high expression of PD-L1 in MPNST tumor cells.IHC staining revealed that aberrant T lymphocytes infiltrated the plexiform neurofibroma and MPNST tumor tissues.Conclusion These results indicate that immune checkpoint mechanisms may play a pivotal role in the development of NF1-related tumors,and immune checkpoint inhibitors may be effective for managing neurofibromas and MPNSTs.Combined therapy with other molecular agents may be explored in the future.
文摘The objectives of this study were to assess the safety and efficacy of intralesionally administered diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This was a proof-of-concept, prospective, safety and efficacy study of the effect of intralesionally administered diclofenac 25 mg/ml given once a week to 3 target cutaneous neurofibromas for 4 consecutive weeks. Overall, there was no significant change in neurofibroma size. During the study, some treated lesions developed signs of necrosis and fell off after a few weeks, but none of the control neurofibromas fell off. There were no significant changes in patient’s vital signs. A few adverse events occurred, mostly at the injection sites. During the study, some neurofibromas developed necrosis after the diclofenac injections and eventually detached from the patient. Overall, diclofenac was well tolerated, suggesting minimal systemic exposure, which required confirmation and further studies, including bioavailability analysis.