Disease relevance of Neurofibromatoses

• A hallmark clinical feature of neurofibromatosis 1 (NF1) is multiple dermal neurofibromas, benign tumours that typically appear in early adolescence and increase in numbers throughout life [1].
• The gene responsible for the hereditary disease neurofibromatosis type 1 (NF1) has been well characterized as a regulator of Ras protein activity [2].
• Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation [3].
• We show that the activation of ERK and the proliferation of human schwannoma cells bearing a loss-of-function mutation in the neurofibromatosis 2 (NF2) gene require MLK3 [4].
• Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis [5].

Psychiatry related information on Neurofibromatoses

• PARTICIPANTS: Patients with neurofibromatosis type 1, epilepsy, or Tourette syndrome diagnosed using traditional clinical criteria; controls without disease; and controls with neurologic disease [6].
• Large deletions of the NF1 locus occur in 5 to 10% of patients with neurofibromatosis and are commonly associated with specific additional abnormalities characterized by mental retardation, dysmorphic features, and intellectual impairment [7].
• Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay [8].

High impact information on Neurofibromatoses

• Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin [9].
• The gene for neurofibromatosis type 1 (NF1) encodes neurofibromin, a protein that negatively regulates signals transduced by Ras proteins [10].
• The neurofibromatosis 2 gene (NF2) has recently been isolated and predicted to encode a novel protein related to the moesin-ezrin-radixin family of cytoskeleton-associated proteins [11].
• A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor [12].
• A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor [13].

Chemical compound and disease context of Neurofibromatoses

• DNA diagnosis of neurofibromatosis 2. Altered coding sequence of the merlin tumor suppressor in an extended pedigree [14].
• The GTPase stimulatory activities of the neurofibromatosis type 1 and the yeast IRA2 proteins are inhibited by arachidonic acid [15].
• C-->U RNA editing of neurofibromatosis 1 (NF1) mRNA changes an arginine (CGA) to a UGA translational stop codon, predicted to result in translational termination of the edited mRNA [16].
• Mutations of this lysine were detected in samples from a neurofibromatosis patient as well as from cancer patients [17].
• Six dermal neurofibromas obtained from 5 patients with neurofibromatosis were dissociated and the cells were plated on polylysine-coated glass [18].

Biological context of Neurofibromatoses

• Simultaneous analysis of D22S1 and IGLV DNA markers for coinheritance with neurofibromatosis 2 indicates that the locus for the disease is near the center of the long arm of chromosome 22 (22q11.1----22q13.1) [19].
• Genetic and biochemical data support the hypothesis that NF1 functions as a tumor-suppressor gene in immature myeloid cells, but inactivation of both NF1 alleles has not been demonstrated in leukemic cells from patients with neurofibromatosis type 1 [10].
• A domain of the neurofibromatosis gene product (NF1) that has sequence similarity to the catalytic domain of Ras-GAP and to yeast IRA gene products also has a specific stimulatory activity toward p21ras GTPase [20].
• By hybridization of the genomic clone to metaphase cells, we have localized the human OMgp gene to chromosome 17 bands q11-12, a region to which the neurofibromatosis type 1 gene has been previously mapped [21].
• In a control experiment, the method was able to identify cDNA clones for the neurofibromatosis type 1 (NF1) gene using a probe generated from a YAC in the region [22].

Anatomical context of Neurofibromatoses

• Cutaneous neurofibromas, characteristic lesions of neurofibromatosis 1, are composed of an abundant extracellular matrix and nerve connective tissue-derived cell types: Schwann cells, perineurial cells, and fibroblasts [23].
• Germ-line NF2 mutations and disease severity in neurofibromatosis type 2 patients with retinal abnormalities [24].
• Immunolocalization of a glycosylphosphatidylinositol-specific phospholipase D in mast cells found in normal tissue and neurofibromatosis lesions [25].
• The neurofibromatosis type 1 gene product neurofibromin enhances cell motility by regulating actin filament dynamics via the Rho-ROCK-LIMK2-cofilin pathway [26].
• The neurofibromatosis 2 tumour suppressor merlin/schwannomin is structurally related to the ezrin-radixin-moesin family of proteins, which anchor actin cytoskeleton to specific membrane proteins and participate in cell signalling [27].

Gene context of Neurofibromatoses

• The neurofibromatosis type 1 (NF1) protein contains a region of significant sequence similarity to ras p21 GTPase-activating protein (GAP) and the yeast IRA1 gene product [28].
• Neurofibromin is the product of the NF1 gene, whose alteration is responsible for the pathogenesis of neurofibromatosis type 1 (NF1), one of the most frequent genetic disorders in man [29].
• The most frequent causes of phaeochromocytoma susceptibility are von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2), the newly delineated phaeochromocytoma-paraganglioma syndrome and, less commonly, neurofibromatosis type 1 [30].
• The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate [31].
• RFLP typing of members of a neurofibromatosis type 2 (NF2) family suggested that affected individuals were hemizygous at the neurofilament heavy chain (NEFH) locus, possibly as a result of a disease-associated deletion [32].

Analytical, diagnostic and therapeutic context of Neurofibromatoses

• Multicolor in situ hybridization also excluded the possibility of pericentric inversions in two unrelated patients with CMT1 and neurofibromatosis type 1 [33].
• Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping [34].
• Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis [35].
• A genetic study of neurofibromatosis type 1 (NF1) in south-western Ontario. II. A PCR based approach to molecular and prenatal diagnosis using linkage [36].
• Denervation in von Recklinghausen's neurofibromatosis (NF-1) leads to fewer and smaller neurofibromas [37].

References