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NF (Neurofibromatosis type 1 (NIH, Boyd), Molecular Characterization and…

- - - - 8 branches, now blurred
        
        1 & 2 are constant
        
        3 = schawnn-omatosis
        
        2 hits vestibular nerves (ears)
        
        7 = schwannomas without other NF 1/2 sympts
        
        5 = "segmental NF1"
        
        6 = "familial cafe-au-lait spots"
        
        4 = atypical NF symptoms
        
        8 = "not otherwise specified"
      - NFI gene discovered in 1990
        
        Autosomal dominant
        
        ~100% penetrance by 20y/o
        
        Nonmosaic, segmental, generalized, or gonadal (mosaics)
        
        segmental = select regions of body effected
        
        Even if gonads are unaffected, NF may still be transmitted
        
        1 more item...
        
        generalized = nonmosaic, but WBCs have normal NF gene
        
        Only oocytes/spermatozoa carry NF mutation
        
        Very rare, likely cause for child with 2degree relatives with NF and NF themselves, but absent in parents
        
        Inheritance patterns: ~50% inherited, ~50% spontaneous mutation
        
        Fmailial inheritance still results in a wide range of manifestations
        
        locus: chromosome 17q11.2
        
        60 exons @ 300+kbp
        
        Most mutations were found to be caused by early ceasation of translation of neurofibromin
        
        Codes for neufobrfibromin
        
        Tumor supressor in Nerve cells and melanocytes
        
        Regulates ras-GTP activity of GTPase-activating proteins
        
        Regulating cell proliferation and differentiation
        
        1 more item...
        
        diagnostic criteria (at least 2)
        
        Of 1900 cases: 54% by age 1; 97% by 8, 100% by 20.
        
        Large allele size and lack of consistent hotspots for mutation
        
        But >95% of inherited and spontaneous cases had NF1 mutations
        
        1 more item...
        
        Six of more café-au-lait macules (spots)
        
        2+ freckles in the axillary of inguinal regions
        
        2+ neurofibromas or 1 plexiform
        
        Optic gliomas, unilaterally or bilaterally
        
        Osseous legions including dysplasia of the sphenoid bone and thinning of bone cortices
        
        A first-degree (mother, father, direct sibling, or offspring) relative with NF1
        
        2+ Lisch nodules
- - - - The microdeletions are believed to be linked with issues with cells descending from the neural crest.
  - - - Seven of ten were unrelated, details on the other 3 is unspecified
        
        A long-range BAC/PAC map was sussed out around the NF1 locus.
        
        5 or seven had nigh identical proximal and distal end points
        
        Each lost 11 functional genes
        
        5 of 6 showed deletion on the maternal chromosome
        
        5 of 6 (7?! tbd... part 2, maybe?)
        
        Resulting in multi-hemizygosity
        
        BUD was a paternal deletion
      - Multiple BAC & PAC sequences of chromosome 17 were collected from multiple institutes to create a complete map of the NF1 gene
        
        True overlap of the sequences were confirmed with multiple PCR tests
        
        Lymphocytes from the 7 were collected and transformed by the Epstein-Barr virus
        
        We gave them mono nucleosis
        
        Metaphase spreads were collected
        
        proximal end
        
        5 of 7 showed flourescent markers for R-271K11, but only one homologue showed for 2309P3
        
        Region 2349P21 was found, and for all 5, proximal deletion started within a small boundary of it.
        
        1 more item...
        
        Distal end
        
        6 of showed a similar slim deletion margin
        
        BUD was the major exception
        
        1 more item...
        
        4 of 7 carried germ-line deletions into the centromere and beyond D17S57 (BUD)