Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurofibromatosis 1 gene (NF1) is a tumor suppressor gene and the product of which down-regulates Nras protein by its GTPase activating protein-related domain (NF1-GRD). Although the incidence of NF1 mutation was reported to be rare in the chronic phase of myelodysplastic syndrome (MDS), there have been no previous reports on its configuration in patients showing the disease progression. We examined NF1 in 50 patients with MDS including 9 who had progressed to more advanced stages and 16 to acute leukemia. Six patients had an Nras mutation. We carried out allele specific restriction analysis (ASRA) to detect a mutation at the first nucleotide A of codon 1423 (AAG), a mutational hot spot. We also employed a polymerase chain reaction mediated single strand conformation polymorphism (PCR-SSCP) method to confirm the result of ASRA and to detect a point mutation in other sequences of FLR exon. In consequence, ASRA disclosed wild type configuration and PCR-SSCP showed no aberrant band in any sample examined whether the samples harboured an Nras mutation or not. We conclude that NF1 mutation does not play a crucial role in the development and the progression of MDS.
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PMID:Neurofibromatosis 1 gene (NF1) mutation is a rare genetic event in myelodysplastic syndrome regardless of the disease progression. 759 22

We report the case of a 14-month-old boy with myelodysplastic syndrome (refractory anemia with blast excess) and bone marrow monosomy 7. Within 2 years after presentation hematological remission gradually occurred without any chemotherapy. After the patient had received three transfusions within the first 4 months, red cell production normalized. However it took 18 more months for neutropenia to resolve. The patient is well 34 months after the first presentation. Molecular analysis of the bone marrow blasts showed no mutations of the ras genes or of the FLR-exon of the NF-1 gene. To our knowledge this is the first report of monosomy 7 syndrome with spontaneous hematological remission.
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PMID:Spontaneous hematological remission in a boy with myelodysplastic syndrome and monosomy 7. 805 84

A mutational hotspot in the neurofibromatosis 1 (NF1) gene has recently emerged from the analysis of different malignancies including one patient with myelodysplastic syndrome (MDS). In these cases, Lys 1423 in the GTPase-activating protein (GAP)-related domain of NF1 is substituted which causes a significant reduction of intrinsic GAP activity. We studied 57 MDS patients and 27 cases of acute myelocytic leukemia (AML) for mutations at codon 1423 in the so-called FLR exon of NF1 by an assay based on restriction enzyme digestion. We investigated the entire FLR exon and its flanking intron sequences using single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products and sequencing. None of the cases exhibited a codon 1423 mutation. However, a patient with chronic myelomonocytic leukemia (CMML) showed a 3 bp deletion within the splice acceptor region in front of the FLR exon. These data suggest that NF1 exon FLR mutations contribute infrequently to the development of MDS and AML.
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PMID:Mutations within the FLR exon of NF1 are rare in myelodysplastic syndromes and acute myelocytic leukemias. 832 Oct 21