• The condition may be inherited as an autosomal dominant condition or occur as a new mutation. (wikipedia.org)
  • An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. (edu.au)
  • A group of disorders characterized by an autosomal dominant pattern of inheritance with high rates of spontaneous mutation and multiple neurofibromas or neurilemmomas. (edu.au)
  • Legius syndrome , initially described as a neurofibromatosis type 1-like syndrome , is a rare autosomal dominant disorder Opens in new window characterized by multiple café-au-lait macules associated with changes in skin coloring (pigmentation). (viquepedia.com)
  • The interaction of neurofibromin and SPRED1 was described comprehensively, providing functional insight that will help in the interpretation of pathogenicity of certain missense variants identified in NF1 and Legius syndrome patients. (escholarship.org)
  • Legius syndrome , caused by SPRED1 mutations, has phenotypic overlap with neurofibromatosis type 1 (NF1) Opens in new window , but the phenotype is milder (Table X-1). (viquepedia.com)
  • One of the quintessential examples having long-range allosteric regulation is the ternary complex, SPRED1-RAS-neurofibromin type 1 (NF1, a RAS GTPase-activating protein), in which SPRED1 facilitates RAS-GTP hydrolysis by interacting with NF1 at a distal, allosteric site from the RAS binding site. (bvsalud.org)
  • Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. (wikipedia.org)
  • A number of genetic mutations can result in Noonan syndrome. (wikipedia.org)
  • RASopathies are a family of genetic disorders caused by mutations in enzymes that modulate the activity of the MAPK pathway , a group of enzymes which is also one of the most important chemical pathways impacted by the fibroblast growth factor receptor 3 (FGFR3) mutation in achondroplasia (reviewed here ). (treatingachondroplasia.com)
  • Mutations in the NF1 gene cause the familial genetic disease neurofibromatosis type I, as well as predisposition to cancer. (bvsalud.org)
  • Noonan syndrome has also been shown to be caused by mutations in KRAS and PTPN11 genes [5] . (bionity.com)
  • Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary malformation syndrome (MCAP) - pure coincidence? (genomeweb.com)
  • Skin signs and symptoms in Noonan syndrome include lymphedema (lymph swelling of the extremities), keloid formation, excessive scar formation, hyperkeratosis (overdevelopment of outer skin layer), pigmented nevi (darkly pigmented skin spots), and connective tissue disease. (wikipedia.org)
  • Patients present with Legius syndrome have multiple café-au-lait spots Opens in new window , which are flat patches on the skin that are darker than the surrounding area. (viquepedia.com)
  • Typical NF1-associated features such as neurofibromas, iris Lisch nodules, malignant peripheral nerve sheath tumors, optic pathway gliomas, and typical osseous lesions (sphenoid wing dysplasia, pseudarthrosis, and vertebral body dysplasia) are not reported in Legius syndrome. (viquepedia.com)
  • Descriptive detail in intelligence and behavior has been reported in 15 children with Legius syndrome (Denayer et al. (viquepedia.com)
  • Legius syndrome is associated with mutations Opens in new window in SPRED 1 gene, a gene that encodes a protein that operates in the same biological pathway as the NF1 gene product. (viquepedia.com)
  • Thus Legius syndrome is a member of the RASopathies. (viquepedia.com)
  • Legius syndrome is the result of increased activity of the Ras/MAPK pathway in a number of cell types. (viquepedia.com)
  • Café-au-lait macules Opens in new window in individuals with Legius syndrome result from biallelic SPRED 1 inactivation in melanocytes. (viquepedia.com)
  • The diagnosis of Legius syndrome is suspected in patients with multiple café-au-lait maculae with or without freckling and no other NF1 diagnostic criteria in whom an NF1 mutation was excluded by mutation analysis (Messianen et al. (viquepedia.com)
  • The NF1 gene product, neurofibromin, is a GTPase-activating protein and acts as a tumor suppressor by negatively regulating the small GTPase, Ras. (bvsalud.org)
  • Noonan syndrome is a type of RASopathy, the underlying mechanism for which involves attenuation of the RAS/MAPK cell signaling pathway. (wikipedia.org)
  • SPRED 1 is a negative regulator of the Ras/MAPK pathway, and SPRED 1 mutations result in decreased inhibition of the pathway. (viquepedia.com)
  • Noonan syndrome is the second most common syndromic cause of congenital heart disease. (wikipedia.org)
  • Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy. (genomeweb.com)
  • The condition was named after American pediatric cardiologist Jacqueline Noonan, who described her first case in 1963. (wikipedia.org)
  • [2] The condition was first described in 1883 and was named after American pediatric cardiologist Jacqueline Noonan, who described further cases in 1963. (handwiki.org)
  • Whole-exome sequencing improves mutation detection in a diagnostic epidermolysis bullosa laboratory. (genomeweb.com)
  • The most common signs leading to the diagnosis of Noonan syndrome are unique facial characteristics and musculoskeletal features. (wikipedia.org)
  • The facial characteristics are most prominent in infancy, becoming less apparent with age in many people with Noonan syndrome. (wikipedia.org)
  • Therefore it is thought that dysregulation of this pathway during development is responsible for many of the clinical features of this syndrome [6] . (bionity.com)
  • Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation status by next generation sequencing: findings from the CAPRI-GOIM trial. (genomeweb.com)
  • A 12-year-old girl with Noonan syndrome, displaying typical webbed neck and double structural curve with rib deformity. (handwiki.org)
  • However, structural insights into neurofibromin activation remain incompletely defined. (bvsalud.org)
  • Some of the characteristic features of Noonan syndrome include a large head with excess skin on the back of the neck, low hairline at the nape of the neck, high hairline at the front of the head, triangular face shape, broad forehead, and a short, webbed neck. (wikipedia.org)
  • Abnormal features of Noonan syndrome at the age of 3 months: Note the eyebrow slant and left-side eyelid dropping. (handwiki.org)
  • Abnormal features of Noonan syndrome at the age of 3 months: Note the low-set, posteriorly rotated, and abnormally formed ear. (handwiki.org)
  • Macrocephaly Opens in new window was present in several individuals as well as a Noonan-like Opens in new window facial morphology. (viquepedia.com)
  • Dominant mutant alleles of SOS1 have recently been found to cause Noonan syndrome [3] and Hereditary Gingival Fibromatosis type 1 [4] . (bionity.com)
  • Here, we provide cryoelectron microscopy (cryo-EM) structures that reveal an extended neurofibromin homodimer in two functional states: an auto-inhibited state with occluded Ras-binding site and an asymmetric open state with an exposed Ras-binding site. (bvsalud.org)
  • Our findings suggest a role for nucleotides in neurofibromin regulation and may lead to therapeutic modulation of Ras signaling. (bvsalud.org)
  • Neurofibromin-1 (NF1) is a large, multidomain tumour suppressor encoded by the NF1 gene. (bvsalud.org)
  • Biochemically, these mutations have been shown to similarly effect aberrant activation of the catalytic domain towards Ras-GTPases. (bionity.com)
  • The final adult height of individuals with Noonan syndrome is about 161-167 cm in males and 150-155 cm in females, which approaches the lower limit of normal. (wikipedia.org)
  • ALK fusion and its association with other driver gene mutations in Finnish non-small cell lung cancer patients. (genomeweb.com)
  • Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. (escholarship.org)