This report describes general characteristics of neurofibromatosis, type 1 (NF1); NF1 is inherited as an autosomal dominant. The human gene implicated in this disease is NF1, which encodes a tumor suppressor protein that appears to function as a regulator of the Ras signal transduction pathway. The NF1 gene is also associated with neurofibromatosis-Noonan syndrome (OMIM:601321), juvenile myelomonocytic leukemia (OMIM:607785), neurofibromatosis, familial spinal (OMIM:162210), and Watson syndrome (OMIM:193520). There is a single fly ortholog, Nf1, for which classical amorphic and loss of function alleles, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of the human gene Hsap\NF1 have been introduced into flies, including wild-type NF1 and NF1 genes carrying mutational lesions. Experiments using human Hsap\NF1 mutations and partial deletions, expressed in flies amorphic for Dmel\Nf1, show that separate domains of NF1 control the different adenylyl cyclase pathways observed in flies.
Variant(s) implicated in human disease tested (as transgenic human gene, NF1): the L847P, R1276P, R1391S (R1412S) and K1423E (K1444E) variant forms of the human gene have been introduced into flies. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): R1320P in the fly Nf1 gene (corresponds to R1276P in the human NF1 gene).
Animals that are homozygous for amorphic allele(s) of Dmel\Nf1 are smaller than wild-type, have a shorter lifespan, exhibit reduced tolerance for various stress conditions, and lack circadian locomotor rhythmicity. An increased frequency of attention deficit hyperactivity disorder and sleep disorders have been observed in individuals with neurofibromatosis 1; these aspects of the disease have also been investigated using Nf1 loss-of-function genotypes in flies. Physical and genetic interactions of the Dmel\Nf1 protein product have been described; see below and in the FlyBase gene report for Nf1.
[updated Oct. 2017 by FlyBase; FBrf0222196]
[NEUROFIBROMATOSIS, TYPE I; NF1](https://omim.org/entry/162200)
[NEUROFIBROMIN 1; NF1](https://omim.org/entry/613113)
Neurofibromatosis type I is characterized by cafe-au-lait spots, Lisch nodules in the eye, and fibromatous tumors of the skin. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors. [from OMIM:162200, 2016.3.17]
Neurofibromatosis type 1 (NF1) is characterized by the development of multiple benign neurofibromas and areas of hypo- or hyperpigmentation of the skin. Areas of abnormal pigmentation typically include cafe-au-lait spots (pale tan or light brown discolorations) on the skin of the trunk and other regions as well as freckling, particularly under the arms and in the groin area. Such abnormalities of skin pigmentation are often evident by one year of age and tend to increase in size and number over time. At birth or early childhood, affected individuals may have relatively large benign plexiform neurofibromas. Individuals with NF1 may also develop Lisch nodules (benign tumor-like nodules of the colored regions of the eyes) or tumors of the optic nerves (second cranial nerves). More rarely, affected individuals may develop certain malignant tumors. NF1 may also be characterized by macrocephaly and relatively short stature. Additional abnormalities may also be present, such as seizures; learning disabilities; speech difficulties; hyperactivity; and skeletal malformations, including scoliosis, bowing of the lower legs, and improper development of certain bones. In individuals with NF1, associated symptoms and findings may vary greatly in range and severity from case to case. Most people with NF1 have normal intelligence but learning disabilities appear in about 50% of children with NF1. [from NORD, NeurofibromatosisType 1 (NF1), 2016.3.17]
NF1 product stimulates the GTPase activity of Ras and may regulate Ras. [from UniProt, P21359 (NF1_human), 2016.4.26] NF1 appears to function as a negative regulator of the ras signal transduction pathway. [from Entrez Gene, NF1 (human), 2016.4.26]