http://www.charite.de/ch/medgen/eumedis/embryology04/neurocutan-disorders.html
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NF1 Gene


Cloned in 1990 Over 300kb of genomic DNA, 50 exons Very large and complicated, and genetic changes can be very small and subtle A missense mutation in GAP-Related Domain is one way NF1 is inactivated - usually a mutation that causes a charge inversion; mostly change from Lysine to something like Glutamine in protein
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Neurofibromatosis Type I
Among most common neurogenetic disorders -It is heritable; all affected members of family have same form of NF Affects 1 in 3,500

/id/int_id_win.html
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Neurofibromatosis Type I





Affects peripheral nerves brain, and spinal cord More active as get older In adolescence, also find learning disabilities in reading, math, trouble following directions, and paying attention All racial and ethnic backgrounds Symptoms vary person to person
NF1 Gene


NF1 is a tumor suppressor gene NF1 is located on Chromosome 17 long arm
- NF2 on other hand is located on Chromosome 22

NF1 gene encodes the prote et al, The Embo Journal, 1998, Vol. 17 6 cc.oulu.fi/~anatwww/ NF/Neurofibromin/Ras.jpg
NF1 Gene Inactivation (Loss of Function)
50% of cases inherited from parent, other 50% of cases start out as a new NF1 mutation in sperm or egg that makes the child All cell types are initially NF+/- until a subpopulation of Schwann cells undergo LOH and become NF-/ Bi-allelic inactivation in Schwann cells causes the lack of expression of Neurofibromin protein - Schwann cells are the initiating cells in neurofibroma formation So, NF1 behaves as a dominant trait phenotypically, but is still recessive genotypically
European Genetics Foundation http://www.charite.de/ch/medgen/eumedis/embryolog y04/neurocutan-disorders.html
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/exp/int_exp _wcn.html

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Whereas NF2 affects only 1 in 40,000
Diagnosis based on any 2 of the following clinical criteria: - Greater than or equal to 6 café-au-lait spots - Freckles underarm or groin - Greater than or equal to 2 neurofibromas, or 1 plexiform neurofibroma - Iris Lisch nodules identified by ophthalmologist - Tumor of optic nerve called optic pathway glioma (in astrocytes) - Bone deformities (i.e. around eye, tibia) - First degree relative (parent, sibling, or child)
NF1: Tumor Suppressor Gene
Presentation by Hana Masood
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Overview of Presentation

Disease – Neurofibromatosis Type I NF1 Gene Protein - Neurofibromin Protein Function – RasGAP Biological Role – Active in Ras Pathway NF1 gene and Neurofibromin Role in Cancer