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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract 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. This mutation removes the 84 by of exon 3 precisely from the cDNA. Genomic Southern blots revealed a larger deletion with breakpoints within the introns flanking exon 3. This mutation suggests that the amino-terminal region of neurofibromin is functionally significant. When using this mutation to distinguish the wild type and mutant alleles, their expression could be analysed in neurofibroma fibroblasts, melanocytes from the unaffected skin, and those from a café-au-lait macule. In all these cell types, the products of both alleles were detected, confirming similar results obtained with a different NFl gene mutation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 93 (1994), S. 481-482 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We describe an RsaI polymorphism in the transcribed region (exon 5) of the neurofibromatosis type 1 (NF1)-gene
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature genetics 6 (1994), S. 331-331 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Sir — After the cloning of the neurofibromatosistype 1 (NF1) gene in 1990 1–3, numerous groups began to search for causative mutations. Although several hundred patients were included in studies carried out by the members of the NNFF International NF1 Genetic Analysis Consortium, only ...
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 291 (1999), S. 312-317 
    ISSN: 1432-069X
    Keywords: Key words NF1 ; M. Recklinghausen ; Melanocytes ; Neurofibromin half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neurofibromatosis type 1 (NF1) is a common autosomal dominantly inherited disorder characterized by neurofibromas and café-au-lait macules. Most of the NF1 gene germline mutations result in a reduction in the level of neurofibromin. As shown recently, the neurofibromin level can be regulated posttranslationally through alteration of the protein half-life. This raises the question as to whether this type of regulation is also operating in cultured melanocytes of NF1 patients especially in melanocytes derived from café-au-lait macules. In melanocytes cultured without phorbol 12-myristate 13-acetate (PMA) the neurofibromin half-lives were 24 h (healthy controls, MC), 26 h (apparently healthy skin of NF1 patients, MNFS) and 25 h (café-au-lait macules of NF1 patients, MNFC). In PMA-stimulated cells the neurofibromin half-lives were 68 h (MC) and 73 h (MNFS) whereas it was 45 h in melanocytes derived from NF1 café-au-lait macules. The amount of NF1 mRNA was not altered under these culture conditions as shown by competitive RT-PCR. We speculate that this regulation is involved in the formation of some NF1 symptoms, for instance in the formation of café-au-lait macules.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-069X
    Keywords: Neurofibromatosis type 1 (NF1) ; Melanocyte culture ; NF1 Gene ; Café-au-lait macules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neurofibromatosis type 1 (NF1) is characterized by clinical features that primarily affect tissues derived from the neural crest (neurofibromas, café-au-lait macules). Because aberrant regulation of alternative splicing in the NF1 gene transcript may be of functional significance, cultured melanocytes from café-au-lait macules (CALM), as an example of benign NF1 lesions, were examined for the expression of the different alternative splice products of this gene. Both kinds of NF1 messengers (type 1 and 2) were found not only in CALM melanocytes but also in keratinocytes, fibroblasts and blood cells. Except in blood cells, there was a predominance of the type 2 transcript. Melanocytes from NF1 patients and healthy donors showed similar expression patterns under several culture conditions. Our results suggest that the development of CALM does not correlate with a switch in the ratio of type 1 to type 2 NF1 messenger RNA.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Key words Expression ; NF1 ; Tumor ; Brain ; Neurofibroma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The close association of neurofibromatosis type 1 (NF1) with gliomas raises the question of whether the NF1 gene may be involved in the pathogenesis of sporadic astrocytic brain tumors. However, no frequent mutations within NF1 have been described in these tumors. Recent data on a limited series of gliomas indicate that NF1 expression may even be increased, thereby questioning the role of NF1 as a tumor suppressor in astrocytomas. In the present study, we examined the expression of NF1 in a series of 96 tumors including astrocytomas, meningiomas and plexiform neurofibromas. NF1 RNA transcription levels were compared to those of the reference genes B2M, ACTB and GAPD. The expression of OMGP, which is interposed in the NF1 gene, served as an additional control. NF1 expression did not significantly diverge among different malignancy stages of astrocytomas. As expected, the plexiform neurofibromas showed only very low NF1 expression. A striking finding was the highly variable expression of those genes selected to serve as references. While B2M and ACTB exhibited comparable levels of expression within different grades of astrocytomas and meningiomas, GAPD showed an inverse pattern in these tumors. In conclusion, NF1 expression is strongly reduced in NF1-associated plexiform neurofibromas but not in astrocytic tumors. The significant differences between B2M, ACTB and GAPD transcript levels brings into question the common practice of defining gene expression as a ratio between the transcripts of interest and those of these reference genes.
    Type of Medium: Electronic Resource
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