• A number of genetic mutations can result in Noonan syndrome. (wikipedia.org)
  • Variants (also known as mutations) in one of several genes can cause Noonan syndrome with multiple lentigines. (medlineplus.gov)
  • Background Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). (bmj.com)
  • The genetic mutations that alter the signaling pathways involved in cardiac development have been implicated in approximately 30 percent of the defects associated with congenital heart diseases," explains the study's senior author Maria Kontaridis, PhD, a scientist in the Division of Cardiovascular Medicine at BIDMC and Assistant Professor of Medicine at Harvard Medical School. (scienceblog.com)
  • Kontaridis's lab investigates LEOPARD syndrome and Noonan syndrome, two of a cluster of congenital diseases known as "RASopathies," which are the result of defects caused by mutations in genes in the RAS signaling pathway. (scienceblog.com)
  • Mutations in the PTPN11 (non-receptor protein tyrosine phosphatase type 11) gene are responsible for virtually all cases of LEOPARD syndrome and about half of the Noonan syndrome cases, notes Kontaridis. (scienceblog.com)
  • By creating an LS mouse model that reproduced features of the human disorder, the Kontaridis group found that the mutations in PTPN11 that cause LEOPARD syndrome are distinct, and lead to a loss of phosphatase activity and hyperactivation of the AKT/mTOR pathway - which leads to the development of hypertrophic cardiomyopathy. (scienceblog.com)
  • PTPN11 Mutations in the Ras-MAPK Signaling Pathway Affect Human White Matter Microstructure. (stanford.edu)
  • Germline activating mutations to the PTPN11 gene cause overactivation of the Ras-Mitogen-Activated Protein Kinase pathway. (stanford.edu)
  • Activating mutations cause Noonan syndrome (NS), a developmental disorder associated with hyperactivity and cognitive weakness in attention, executive function, and memory. (stanford.edu)
  • Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. (sdbonline.org)
  • This study found that CSW loss-of-function mutations extended life span by interacting with components of the insulin signaling pathway and impairing AKT activity in adult flies. (sdbonline.org)
  • Noonan and Noonan-like syndromes are multisystem genetic disorders, mainly with autosomal dominant trasmission, caused by mutations in several genes. (biomedcentral.com)
  • Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. (unifesp.br)
  • PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. (unifesp.br)
  • Contribution of gene mutations to Silver-Russell syndrome phenotype: multigene sequencing analysis in 92 etiology-unknown patients. (cdc.gov)
  • Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations. (cdc.gov)
  • Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. (antikoerper-online.de)
  • For many congenital heart diseases, such as Noonan Syndrome, the link between the genetic changes (mutations) and the heart malformations have not yet been fully understood. (mbexc.de)
  • Scientists at the Heart Center of the University Medical Center Göttingen (UMG) and the Cluster of Excellence "Multiscale Bioimaging" (MBExC) have for the first time been able to identify the link between the underlying gene mutations and the development of heart muscle thickening (heart hypertrophy) for the congenital heart disease Noonan Syndrome. (mbexc.de)
  • Noonan syndrome (NS) belongs to a group of genetic disorders called RASopathies that are caused by germ-line mutations that affect genes residing along the canonical RAS-MAPKinase signaling pathway. (armi.org.au)
  • 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)
  • 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)
  • Noonan syndrome is a type of RASopathy, the underlying mechanism for which involves attenuation of the RAS/MAPK cell signaling pathway. (wikipedia.org)
  • The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. (stanford.edu)
  • Fragile X syndrome (FXS) is likewise characterized by elevated MAPK/ERK signaling. (sdbonline.org)
  • This suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS and CFCS rather than specific mutation effects. (unifesp.br)
  • MAPK Pathway Phospho Antibody Array features 185 highly specific antibodies related to the MAPK pathway. (bnwax.com)
  • The facial characteristics are most prominent in infancy, becoming less apparent with age in many people with Noonan syndrome. (wikipedia.org)
  • In the eyes, hypertelorism (widely set eyes) is a defining characteristic, present in 95% of people with Noonan syndrome. (wikipedia.org)
  • Up to 20 percent of people with Noonan syndrome with multiple lentigines who have heart problems have a narrowing of the artery from the heart to the lungs (pulmonary stenosis). (medlineplus.gov)
  • People with Noonan syndrome with multiple lentigines can have a distinctive facial appearance. (medlineplus.gov)
  • At birth, people with Noonan syndrome with multiple lentigines are typically of normal weight and height, but in some, growth slows over time. (medlineplus.gov)
  • This slow growth results in affected individuals being shorter than average, although less than half of people with Noonan syndrome with multiple lentigines have significantly short stature. (medlineplus.gov)
  • We collected structural brain MRI and cognitive-behavioral data from 40 pre-pubertal children with Noonan syndrome (NS), caused by PTPN11 (n = 30) or SOS1 (n = 10) variants (age 8.53 ± 2.15, 25 females), and compared them to 40 age- and sex-matched typically developing controls (9.24 ± 1.62, 27 females). (stanford.edu)
  • 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)
  • Noonan syndrome is the second most common syndromic cause of congenital heart disease. (wikipedia.org)
  • Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. (medlineplus.gov)
  • As the condition name suggests, Noonan syndrome with multiple lentigines is very similar to a condition called Noonan syndrome, and it can be difficult to tell the two disorders apart in early childhood. (medlineplus.gov)
  • Not all individuals with Noonan syndrome with multiple lentigines have all the characteristic features of this condition. (medlineplus.gov)
  • The lentigines seen in Noonan syndrome with multiple lentigines typically first appear in mid-childhood, mostly on the face, neck, and upper body. (medlineplus.gov)
  • The remaining individuals with Noonan syndrome with multiple lentigines do not have an identified mutation in any of these four genes. (medlineplus.gov)
  • LEOPARD syndrome affects approximately 200 individuals worldwide and is clinically distinguished by multiple lentigines (freckle-like spots on the skin), as well as craniofacial defects, deafness, and blood abnormalities which can give rise to pediatric leukemias. (scienceblog.com)
  • With the exception of lentigines, Noonan syndrome patients exhibit nearly identical features and pathologies. (scienceblog.com)
  • Noonan syndrome (NS) and NS with multiple lentigines (NSML) cognitive dysfunction are linked to SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) gain-of-function (GoF) and loss-of-function (LoF), respectively. (sdbonline.org)
  • Scientists at the Heart Center of the University Medical Center Göttingen have for the first time found an approach for a personalised therapy option with "gene editing" for the Noonan Syndrome. (mbexc.de)
  • The gene regulates essential signaling pathways for cell differentiation and growth. (mbexc.de)
  • The patient-specific iPS cells of both children, which were recreated in the laboratory, responded immediately to a gene correction using CRISPR/Cas9, the so-called "gene scissors": the signaling pathway activity normalized and the thickening of the heart muscles (hypertrophy) decreased. (mbexc.de)
  • 3 Additional rare autosomal dominant or recessive disorders, such as Smith-Lemli-Opitz syndrome, Timothy syndrome and CHARGE syndrome have been described as associated with autism in clinical reports. (bmj.com)
  • This study identified that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW) , controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. (sdbonline.org)
  • A new online study by Paige Naylor, doctoral candidate at Palo Alto University in California, is recruiting families who has a child with any RASopathy syndrome between the ages of 8-18, and who can communicate in English. (rasopathiesnet.org)
  • A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway. (sdbonline.org)
  • Other musculoskeletal manifestations in Noonan syndrome are associated with undifferentiated connective-tissue disorders which can be associated with joint contractures (tightness) or joint hypermobility (looseness). (wikipedia.org)
  • Our findings in LEOPARD syndrome may additionally provide the first glimpse of a much broader implication - a potential mechanism for the treatment of other, more common congenital hypertrophy disorders. (scienceblog.com)
  • Noonan syndrome is a genetic disease that is associated with developmental disorders. (mbexc.de)
  • 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)
  • These conditions all have similar signs and symptoms and are caused by changes in the same cell signaling pathway. (medlineplus.gov)
  • In addition, the Göttingen researchers found out that the current drug therapy (calcium channel blockers or inhibition of the RAS-MAP kinase signalling pathway) is only partially effective against the symptoms in the heart muscle cells. (mbexc.de)
  • Now a new study showing that the mTOR inhibitor drug rapamycin can reverse cardiac muscle damage in a mouse model of the congenital disease LEOPARD syndrome not only identifies the first possible medical treatment for this rare condition, but also demonstrates the importance of targeted therapies in managing congenital diseases. (scienceblog.com)
  • Our next step will be to test rapamycin in a clinical trial to evaluate the effect of this treatment in humans with LEOPARD syndrome. (scienceblog.com)
  • Noonan Syndrome: Common Molecular Alterations and the Consequences. (cdc.gov)
  • The cause of the overactivation of the RAS-MAP kinase signaling pathway, the pathological enlargement of the cells and the changes in the excitation-contraction coupling of the heart could be explained and a molecular signature of the disease could be constructed. (mbexc.de)
  • In this seminar, I will first present how we used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes to decipher the molecular pathways that underlie HCM in NS. (armi.org.au)
  • 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)
  • Adapter protein that functions as a negative regulator of many signaling pathways that start from receptors at the cell surface. (abcam.com)
  • A fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome was conducted in a Drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. (sdbonline.org)
  • The most common signs leading to the diagnosis of Noonan syndrome are unique facial characteristics and musculoskeletal features. (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)
  • Type V is considered as a distinct entity as, unlike the other types, is usually associated with both cystic renal disease and liver fibrosis (Caroli syndrome). (biomedcentral.com)
  • This pathway is involved in many biological processes, e.g. cell differentiation and cell growth. (mbexc.de)
  • Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels. (cdc.gov)
  • 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)
  • Noonan syndrome patients beyond the obvious phenotype: A potential unfavorable metabolic profile. (cdc.gov)
  • A related study in today's on-line issue of the JCI, by a team of scientists at the University Health Network, Toronto, found that in a mouse model of Noonan syndrome, excessive activity of an enzyme called ERK (a downstream target of the RAS pathway) led to the development of hypertrophic cardiomyopathy, and that treatment with an ERK inhibitor currently being tested as an anti-cancer agent, reversed the cardiomyopathy. (scienceblog.com)
  • YM155 potently kills acute lymphoblastic leukemia cells through activation of the DNA damage pathway. (bnwax.com)
  • Noonan syndrome-like phenotype in a patient with heterozygous ERF truncating variant. (cdc.gov)
  • The most well established of these, including fragile X syndrome, tuberous sclerosis, Rett syndrome, and PTEN mutation account for up to 5% of ASDs. (bmj.com)