Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NEUROFIBROMATOSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed2006

Neurofibromatosis types 1 and 2.

BACKGROUND: Neurofibromatosis types 1 and 2 (NF1 and NF2) are autosomal dominant neurocutaneous disorders with some similarities and many differences. They are frequently discussed together and often confused for one another by clinicians. Both disorders have widely variable presentations and degrees of severity. A thorough understanding of these complex disorders is essential for proper medical management, anticipatory care, and patient education. REVIEW SUMMARY: In this article, the clinical features, genetics, pathogenesis, and management of neurofibromatosis types 1 and 2 are reviewed and compared. CONCLUSIONS: NF1 and NF2 are complex genetic disorders with numerous manifestations and wide phenotypic variability. The complex nature of these disorders requires coordinated multidisciplinary care.

Central Nervous System Neoplasms↗
PubMed2005

Gonosomal mosaicism for a nonsense mutation (R1947X) in the NF1 gene in segmental neurofibromatosis type 1.

Segmental neurofibromatosis type 1 (SNF1), characterized by the regionally limited distribution of neurofibromatosis type 1 (NF1) features, has been attributed to mosaicism for an NF1 gene mutation. The occurrence of classical NF1 in the offspring of a parent with SNF1 suggests that cutaneous mosaicism may be accompanied by gonadal mosaicism. We studied a girl with generalized NF1, and her mother who has SNF1. A recurrent nonsense mutation in exon 31 (R1947X) of the NF1 gene was identified in the lymphocyte DNA of the affected child by denaturing high-performance liquid chromatography and PCR/direct sequencing. DNA sequence analysis failed, however, to identify the R1947X mutation in peripheral lymphocytes, and in keratinocytes and fibroblasts cultured from affected and unaffected skin in the mother. DNA fragments containing exon 31 were then cloned from each cell line and these clones were screened using allele-specific PCR. The R1947X mutation was identified in 29 of 146 clones derived from keratinocytes from the affected region and in 12 of 136 clones derived from fibroblasts from the affected region, but in no clones derived from clinically unaffected tissues. These findings confirm that gonosomal mosaicism can occur in SNF1, with consequent important implications for genetic counselling.

Adult↗
PubMed2006

Clinical and molecular aspects of an informative family with neurofibromatosis type 1 and Noonan phenotype.

Neurofibromatosis-Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndrome, which are separate syndromes. Potential etiologies of NFNS include a discrete syndrome of distinct etiology, co-segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS.

Adolescent↗
PubMed1996

Molecular genetics of neurofibromatosis type 1 (NF1).

Neurofibromatosis type 1 (NF1), also called von Recklinghausen disease or peripheral neurofibromatosis, is a common autosomal dominant disorder characterised by multiple neurofibromas, café au lait spots, and Lisch nodules of the iris, with a variable clinical expression. The gene responsible for this condition, NF1, has been isolated by positional cloning. It spans over 350 kb of genomic DNA in chromosomal region 17q11.2 and encodes an mRNA of 11-13 kb containing at least 59 exons. NF1 is widely expressed in a variety of human and rat tissues. Four alternatively spliced NF1 transcripts have been identified. Three of these transcript isoforms (each with an extra exon: 9br, 23a, and 48a, respectively) show differential expression to some extent in various tissues, while the fourth isoform (2.9 kb in length) remains to be examined. The protein encoded by NF1, neurofibromin, has a domain homologous to the GTPase activating protein (GAP) family, and downregulates ras activity. The identification of somatic mutations in NF1 from tumour tissues strongly supports the speculation that NF1 is a member of the tumour suppressor gene family. Although the search for mutations in the gene has proved difficult, germline mutation analysis has shown that around 82% of all the fully characterised NF1 specific mutations so far predict severe truncation of neurofibromin. Further extensive studies are required to elucidate the gene function and the mutation spectrum. This should then facilitate the molecular diagnosis and the development of new therapy for the disease.

Animals↗
PubMed1996

The detection of contiguous gene deletions at the neurofibromatosis 1 locus with fluorescence in situ hybridization.

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized primarily by the development of multiple neurofibromas and pigmentary changes. The recent identification of contiguous gene deletions in NF1, a previously unrecognized molecular basis for this disorder, raises important questions regarding deletion frequency in the patient population and the role that contiguous genes may play in the physical manifestations of NF1 patients. To facilitate the identification of patients with large NF1 deletions, we have isolated clones carrying large genomic segments from the NF1 locus and tested their efficacy as probes for fluorescence in situ hybridization (FISH). Clone P1-9 spans approximately 65 kb of the NF1 gene, including exons 2-11, and clone P1-12 carries approximately 55 kb of NF1 intron 27B. FISH studies performed with P1-9, P1-12, and a set of overlapping 1F10 cosmid clones mapping telomeric to the NF1 locus identified large deletions in two new neurofibromatosis type 1 patients who, like previously characterized deletion patients, had mildly dysmorphic facial features and large numbers of cutaneous neurofibromas.

Chromosome Aberrations↗
PubMed2002

Clinical features and pathobiology of neurofibromatosis 1.

Neurofibromatosis 1 is a progressive multisystem disorder. The hallmark feature is the occurrence of nerve sheath tumors, neurofibromas. Other features include tumors such as optic gliomas and malignant peripheral nerve sheath tumors. There are also nontumor manifestations, such as skeletal dysplasia and learning disabilities. Since the NF1 gene was identified, much has been learned about the molecular genetics of the disorder; recently, this has led to insights about pathogenesis. Ultimately, it is hoped that this will be translated into specific means of treatment. This review describes the various clinical features of neurofibromatosis 1 and considers them in the context of the pathophysiology of the disorder.

Cell Transformation, Neoplastic↗
PubMed1995

Combined molecular genetic studies of chromosome 22q and the neurofibromatosis type 2 gene in central nervous system tumors.

Monosomy of chromosome 22 or deletions of 22q have been described in meningiomas and astrocytic tumors, the incidence of which is increased in Type 2 neurofibromatosis. Recently, the gene for neurofibromatosis Type 2 (NF2) has been identified at Chromosome 22q12, and a tumor suppression role has been suggested. Because there have been only a few studies of the NF2 gene on central nervous system tumors other than vestibular schwannomas, we investigated the potential role of NF2 as a tumor suppressor gene in a group of sporadic meningiomas and astrocytomas. Forty-four tumors (26 meningiomas and 18 astrocytic tumors of different grades) were screened for NF2 mutations for the entire 17 exons by the polymerase chain reaction-single-strand conformation polymorphism method. In addition, 37 tumors and their respective constitutional deoxyribonucleic acid were analyzed for loss of heterozygosity of 22q alleles by four polymorphic microsatellite markers. Seven inactivating mutations were found in Exons 4, 5, 6, and 10 in 7 of 26 (27%) meningiomas, but none were found in astrocytic tumors. Altogether, 69% of meningiomas and 20% of astrocytic tumors revealed a loss of heterozygosity of 22q markers. All tumors with NF2 mutations showed concurrent loss of alleles on 22q, thus fulfilling Knudson's criteria for tumor suppressor genes in meningiomas. We conclude that inactivation of the NF2 gene is involved in the pathogenesis of a proportion of meningiomas but not in astrocytic tumors. Because many meningiomas and some astrocytic tumors had allelic loss of 22q but intact NF2, there is a possibility that other tumor suppressor genes exist on 22q and may be involved in the pathogenesis of central nervous system tumors.

Adolescent↗
PubMed2001

Tumor suppressor gene regulation of cell growth: recent insights into neurofibromatosis 1 and 2 gene function.

The development of cancer involves a myriad of genetic changes that impact on multiple processes important for the orderly regulation of cell growth and differentiation. Genes whose protein products are disrupted during neoplastic transformation are termed "tumor suppressor genes" (TSGs). Many of these TSGs are associated with familial cancer predisposition syndromes, in which affected individuals have an increased risk of certain malignancies. Studies on the mechanism of action for known TSGs have revealed three intracellular loci of critical importance: environmental sensing and signal initiation, signal propagation and transduction, and cell cycle control. The neurofibromatosis 1 and neurofibromatosis 2 genes are discussed as illustrative examples of tumor suppressors that function at the levels of signal transduction and environmental sensing, respectively.

Animals↗
PubMed1999

[Importance of multidisciplinary consultations for children with neurofibromatosis].

Over a one year period, the multidisciplinary consultation of the Saint-Vincent-de-Paul Hospital for neurofibromatosis examined 26 children. Twenty-two children underwent an ophthalmological examination (21 NF1, 1 NF2). Lisch nodule was the most frequent symptom (12 cases) and corneal nerves were visible in 3 cases. We had only one case of retinal and choroidal hamartoma. Glioma was a frequent symptom (5 cases). Other signs were uncommon. The case of NF2 showed a 3rd nerve palsy and lens droplets. Our evaluation confirms the frequency of Lisch nodules as the most frequent symptom of NF1. The visibility of corneal nerves and hamartoma are suggestive signs. The glioma number fits well with its statistical frequency. One year evaluation of our NF clinic allows us to confirm the relative frequency of the different signs associated with neurofibromatosis. It emphasizes the importance of teaching its diagnosis and follow-up to ophthalmologists.

Adolescent↗
PubMed1992

Neurofibromatosis and central nervous system tumors in childhood.

Neurofibromatosis is a multifaceted disease that often results in tumors of the central nervous system. As our understanding of the molecular biology of the disease improves along with better neuroradiology imaging, surgical instrumentation, and adjunctive care, the management schemes for these patients are evolving. This article reviews what is known about neurofibromatosis, common management problems with respect to the central nervous system, and an approach to the handling of these issues.

Brain↗
PubMed1992

Neurofibromatosis type 2 appears to be a genetically homogeneous disease.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome characterized by the development of vestibular schwannomas and other tumors of the nervous system, including cranial and spinal meningiomas, schwannomas, and ependymomas. The presence of bilateral vestibular schwannomas is sufficient for the diagnosis. Skin manifestations are less common than in neurofibromatosis type 1 (NF1; von Recklinghausen disease). The apparent clinical distinction between NF1 and NF2 has been confirmed at the level of the gene locus by linkage studies; the gene for NF1 maps to chromosome 17, whereas the gene for NF2 has been assigned (in a single family) to chromosome 22. To increase the precision of the genetic mapping of NF2 and to determine whether additional susceptibility loci exist, we have performed linkage analysis on 12 families with NF2 by using four polymorphic markers from chromosome 22 and a marker at the NF1 locus on chromosome 17. Our results confirm the assignment of the gene for NF2 to chromosome 22 and do not support the hypothesis of genetic heterogeneity. We believe that chromosome 22 markers can now be used for presymptomatic diagnosis in selected families. The NF2 gene is tightly linked to the D22S32 locus (maximum lod score 4.12; recombination fraction 0). A CA-repeat polymorphism at the CRYB2 locus was the most informative marker in our families (lod score 5.99), but because the observed recombination fraction between NF2 and CRYB2 was 10 cM, predictions using this marker will need to be interpreted with caution.

Chromosomes, Human, Pair 17↗
PubMed2004

Somatic mitochondrial DNA mutations in neurofibromatosis type 1-associated tumors.

Neurofibromatosis type 1 is an autosomal dominantly inherited disease predisposing to a multitude of tumors, most characteristically benign plexiform neurofibromas and diffuse cutaneous neurofibromas. We investigated the presence and distribution of somatic mitochondrial DNA (mtDNA) mutations in neurofibromas and in nontumor tissue of neurofibromatosis type 1 patients. MtDNA alterations in the entire mitochondrial genome were analyzed by temporal temperature gradient gel electrophoresis followed by DNA sequencing. Somatic mtDNA mutations in tumors were found in 7 of 19 individuals with cutaneous neurofibromas and in 9 of 18 patients with plexiform neurofibromas. A total of 34 somatic mtDNA mutations were found. All mutations were located in the displacement loop region of the mitochondrial genome. Several plexiform neurofibromas from individual patients had multiple homoplasmic mtDNA mutations. In cutaneous neurofibromas, the same mtDNA mutations were always present in tumors from different locations of the same individual. An increase in the proportion of the mutant mtDNA was always found in the neurofibromas when compared with nontumor tissues. The somatic mtDNA mutations were present in the Schwann cells of the analyzed multiple cutaneous neurofibromas of the same individual. The observed dominance of a single mtDNA mutation in multiple cutaneous neurofibromas of individual patients indicates a common tumor cell ancestry and suggests a replicative advantage rather than random segregation for cells carrying these mutated mitochondria.

Base Sequence↗
PubMed1992

Identification of neurofibromatosis type I gene product as an insoluble GTPase-activating protein toward ras p21.

The neurofibromatosis type I (NF1) gene was cloned as a gene whose structural change is closely related to the onset of a neurocutaneous disorder, neurofibromatosis type I. The predicted amino acid sequence of the NF1 gene product shows significant similarity to the catalytic domain of GTPase-activating protein (GAP) for ras p21. This GAP-related domain has been shown to have GAP activity when expressed by recombinant DNA technique, however little is known about the NF1 gene product expressed in tissues. Antibodies against the carboxy terminus and the GAP-related domain of the NF1 gene product were made to identify and characterize NF1 protein expressed in vivo. Both antibodies specifically reacted with a polypeptide with apparent molecular weight of 235 kDa in immunoblot and immunoprecipitation analyses. This 235 kDa protein is detected in brain but not in spleen, thymus, kidney, liver, lung and heart. The subcellular distribution of NF1 and GAP was studied using rat brain extract and was identified by the activity which was inhibited by antibodies against GAP-related domain of NF1 and anti-GAP respectively. The results show that NF1 protein mainly resides in the particulate fraction, in contrast to GAP, which is a soluble protein. We also found that a GAP activity which is not inhibited by anti-NF1 and anti-GAP exists in both the soluble and particulate fractions. The result suggests that there may be another GAP molecule.

Animals↗
PubMed1991

[Central nervous system lesions in neurofibromatosis. Clinical, MRI and histopathological correlations. A trial of classification].

The National Institute of Health Consensus Panel on Neurofibromatosis (NF) recently recognized 2 distinct forms of NF (NF-1 and NF-2) and stated that variant forms may exist. We selected 30 patients who fulfilled the criteria of NF-1 or whose condition was consistent with NF-2. All patients showed pathological magnetic resonance images (MRI), and in 19 cases confirmation was obtained from histopathology. We established correlations between the site and nature of the lesions on the one hand and the diagnostic criteria of NF on the other hand, there by hoping to contribute to a better knowledge and classification of neurofibromatosis. Nineteen patients had only intraparenchymatous lesions of the central nervous system (CNS) and fulfilled the criteria of NF-1; histopathological examination demonstrated pilocytic astrocytoma in 8 cases. Eleven patients showed only extra-axial lesions; 8 of them had criteria suggestive of NF-2, except for familial history. Pathological examination revealed either acoustic, pluriradicular of mixed schwannomas (7/8) or pluriradicular ganglioneuromas (1/8). Two patients had unilateral extra-axial pluriradicular cervical lesions and fulfilled the diagnostic criteria of NF-1; pathological examination revealed neurofibroma in both cases. One female patient had both intra- and extra-axial lesions that fulfilled the criteria of NF-1 and NF-2, suggesting the existence of a mixed form (NF-3).

Adolescent↗
PubMed1995

Neurofibromatosis.

The neurofibromatoses are defined by the presence of café-au-lait macules and neurofibromas and are associated with central and peripheral nervous system tumors. Individuals with neurofibromatosis 1 are at risk for optic nerve gliomas, nerve root and plexi neurofibromas and schwannomas, spinal cord tumors, benign and malignant peripheral nerve sheath tumors, and pheochromocytomas. Individuals with neurofibromatosis 2 are at risk for presenile cataracts, vestibular schwannomas, intracranial and intraspinal meningiomas, and intramedullary spinal cord ependymomas.

Child↗
PubMed1994

Neurofibromatosis type 1.

The authors review the present data on the clinical and molecular aspects of neurofibromatosis type 1 (NF1). In the clinical part attention is given to the frequent observation of learning disabilities in NF1 children. In these children visual-spatial integration deficits and an increased incidence of school performance problems are observed. The NF1 gene is located on chromosome 17 (17q11.2), and is highly conserved across species. Up to now only a limited number of mutations in this gene have been characterized, and this shows a general lack of genotype-phenotype correlation. Evidence is given that the NF1 gene acts as a true tumor suppressor gene and that oncogenesis in NF1 is a complex multistep phenomenon with the second hit in the NF1 gene as the initiating event. The importance of specialized multidisciplinary outpatient clinics for neurofibromatosis is emphasized because of the complexity of follow-up and treatment of these patients.

Child↗
PubMed1994

Specific expression of the neurofibromatosis type 1 gene (NF1) in the hamster Schwann cell.

The gene responsible for neurofibromatosis type 1 (NF1) has sequence homology to the GTPase-activating protein (GAP) and demonstrates GAP activity against ras p21. To study tissue-specific and/or tumor-specific expression of the NF1 gene product, now called neurofibromin, immunostaining and immunoblotting were applied to the N-nitroso-N-ethylurea (ENU)-induced Syrian hamster neurofibromatosis model using polyclonal antibodies against the NF1 fusion protein and a synthetic peptide. Strong expression was observed specific to the Schwann cells of the normal peripheral nerves by immunostaining. Neoplastic Schwann cells showed specific binding of anti-NF1; however, the frequency of positive cells was diminished. Immunoblotting also revealed positive expression of the 250-kd NF1 gene product in the brain, the normal peripheral nerves, and 7 of 14 ENU-induced neurofibromas. Although ENU-induced melanoma and Wilms' tumor were negative for neurofibromin, foci of Schwannian differentiation in both primary and transplanted melanomas were positive. These results suggest that neurofibromin plays some role in differentiation and growth regulation of the Schwann cell.

Animals↗
PubMed1996

Multiple cutaneous plexiform schwannomas. Report of a case and review of the literature with particular reference to the association with types 1 and 2 neurofibromatosis and schwannomatosis.

Plexiform schwannomas are relatively rare, benign peripheral nerve sheath tumors, which usually arise in either the dermis or subcutaneous tissue, although rare cases originate in skeletal muscle or other deep somatic soft tissue sites. These tumors may occur singly or as multiple lesions and may be localized to one anatomic site or diffusely distributed. Rare cases have been associated with "schwannomatosis" as well as type 1 neurofibromatosis (von Recklinghausen's disease). We report an unusual case of multiple cutaneous plexiform schwannomas associated with bilateral acoustic neuromas as well as other intracranial and intraspinal neoplasms. In addition, we examine the relationship between the various forms of cutaneous schwannoma, particularly the plexiform variant, and both types 1 and 2 neurofibromatosis; we also examine several purported cases of schwannomatosis.

Adolescent↗