Disease relevance of Genes, Neurofibromatosis 1

• Sequencing of the neurofibromatosis gene (NF1) revealed a striking similarity among NF1, yeast IRA proteins, and mammalian GAP (GTPase-activating protein) [1].
• Von Recklinghausen's disease is a relatively common familial genetic disorder characterized by inactivating mutations of the Neurofibromatosis-1 (NF1) gene that predisposes these patients to malignancies, including an increased risk for juvenile myelomonocytic leukemia [2].
• Analysis of the GAP-related domain of the neurofibromatosis type 1 (NF1) gene in childhood brain tumors [3].
• Allelic loss at the neurofibromatosis type 1 (NF1) gene locus is frequent in desmoplastic neurotropic melanoma [4].
• In this study, we analysed a protein product of the neurofibromatosis type 1 (NF1) gene, neurofibromin, in human established leptomeningeal cells LTAg2B, in 17 sporadic meningiomas and in a meningioma from a patient affected by NF2 [5].

Psychiatry related information on Genes, Neurofibromatosis 1

• A large deletion (1.5 Mb) encompassing the neurofibromatosis type 1 (NF1) gene in a patient with sporadic NF1 associated with dysmorphism, mental retardation, and unusual ocular and skeletal features [6].

High impact information on Genes, Neurofibromatosis 1

• For example, activating point mutations in RAS genes are found in some patients with juvenile chronic myelogenous leukaemia (JCML), while other patients with JCML show loss of the neurofibromatosis type 1 (NF1) gene, a Ras GTPase activating protein [7].
• For p21ras, two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product [8].
• Progress towards identifying the neurofibromatosis (NF1) gene [9].
• The von Recklinghausen neurofibromatosis (NF1) gene has been mapped to the pericentromeric region of chromosome 17 [10].
• Stable transfection of activated Ha-ras into a number of murine cells correlated with a down-regulation of the expression of the NF1 genes NF1/CTF and NF1/X [11].

Chemical compound and disease context of Genes, Neurofibromatosis 1

• Expression of the GTPase activating domain of the neurofibromatosis type 1 (NF1) gene in Escherichia coli and role of the conserved lysine residue [12].
• We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF1) gene, the guanine triphosphatase (GTPase) activating protein (GAP)-related domain (NF1 GRD), to which the function of tumour suppressor is attributed [13].

Biological context of Genes, Neurofibromatosis 1

• The neurofibromatosis (NF1) gene shows significant homology to mammalian GAP and is an important regulator of the ras signal transduction pathway [14].
• Therefore we analyzed the neurofibromatosis type 1 (NF1) gene region on chromosome 17q11.2, which is characterized by a nonuniform LD pattern and an L1-to-H2 isochore transition [15].
• Site and sequence specific DNA methylation in the neurofibromatosis (NF1) gene includes C5839T: the site of the recurrent substitution mutation in exon 31 [16].
• Similarly, a high SNP density was found in the LCR regions flanking the neurofibromatosis type 1 (NF1) gene, with 80% of SNPs mapping on both LCR copies [17].
• Exon skipping associated with A-->G transition at +4 of the IVS33 splice donor site of the neurofibromatosis type 1 (NF1) gene [18].

Anatomical context of Genes, Neurofibromatosis 1

• We have identified a protein isoform of the neurofibromatosis 1 (NF1) gene (neurofibromin) containing the alternatively spliced exon 9a that is expressed in forebrain neurons [19].
• To test if loss of the neurofibromatosis type 1 gene (Nf1) compromises fibroblast function in vivo following trauma, skin wounding was performed in Nf1 knockout mice [20].
• Increased expression of the neurofibromatosis 1 (NF1) gene product, neurofibromin, in astrocytes in response to cerebral ischemia [21].
• Differential localization of the neurofibromatosis 1 (NF1) gene product, neurofibromin, with the F-actin or microtubule cytoskeleton during differentiation of telencephalic neurons [22].

Associations of Genes, Neurofibromatosis 1 with chemical compounds

• GAP activity of membrane was not solubilized with 0.5% (v/v) triton X-100 and was immunoprecipitated with antibody against carboxy-terminus of neurofibromatosis type 1 (NF1) gene product [23].

Gene context of Genes, Neurofibromatosis 1

• A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity [24].
• INTRODUCTION: Neurofibromatosis type 1 is caused by mutations in the NF1 gene encoding the Ras GTPase activating protein (Ras-GAP) neurofibromin [25].
• The OMgp gene, a second growth suppressor within the NF1 gene [26].
• A new mutation, the first one close to the 5'-end of the neurofibromatosis type 1 (NF1) gene, was found when RNA preparations from various cell types of 15 NF1 patients were analysed by reverse transcription and subsequent multiplex polymerase chain reaction [27].
• Cis-acting sequences spanning: (i) nt -65 to -85 bound NF-Y, an ubiquitous "AACCAAT" box binding factor; (ii) nt -157 to -171 bound a liver-enriched member of the NF1 gene family [NF1Liver (NF1L hereafter)]; (iii) nt -266 to -281 bound the liver specific factor HNF1; and (iv) nt -283 to -288 bound ubiquitous "CCAAT" box binding factor(s) [28].

Analytical, diagnostic and therapeutic context of Genes, Neurofibromatosis 1

• The genomic structure of the Neurofibromatosis Type1 (NF1) gene of Fugu rubripes was investigated by sequence analysis of two overlapping cosmids [29].
• We have characterized two intragenic polymorphisms in the neurofibromatosis type 1 (NF1) gene by direct sequencing of PCR products [30].

References