Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardio-facio-cutaneous syndrome (CFC) is a multiple congenital anomaly disorder characterized by craniofacial dysmorphia, ectodermal abnormalities, congenital heart defects, and developmental and growth delay. Neurological complications associated with CFC remain to be clearly defined. Recent discovery of causative mutations in genes of the MAPK pathway (BRAF, MEK1, and MEK2) now permit accurate molecular diagnosis of CFC. The aim of the study was to characterize neurological features of participants with molecularly-confirmed CFC. Medical records, and laboratory and imaging data were reviewed for 39 mutation-positive individuals with CFC. Participants with a clinical diagnosis of CFC but a negative result on mutation screening of the BRAF, MEK1, and MEK2 genes were excluded from the study. Mean age of participants was 9 years 4 months (range 18 mo-24 y); there were 24 females and 15 males. Mutations in B RA F were present in 32 participants, MEK1 in five, and MEK2 in two participants. Hypotonia, motor delay, speech delay, and learning disability were universally present in this cohort. Macrocephaly was present in 13 participants, ptosis in 11, strabismus in 14, and nystagmus in 11 of the 22 participants who underwent a neurological exam. Corticospinal tract findings were present in seven participants. Ventriculomegaly or hydrocephalus was present in 14 of 32 participants who underwent brain imaging. Other findings on magnetic resonance imaging included prominent Virchow-Robin spaces (n=6), abnormal myelination (n=4), and structural anomalies (n=5). Seizures were present in 15 participants. No specific genotype-phenotype correlation was observed.
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PMID:Neurological complications of cardio-facio-cutaneous syndrome. 1803 35

Fragile X syndrome, caused by the loss of FMR1 gene function and loss of fragile X mental retardation protein (FMRP), is the most commonly inherited form of mental retardation. The syndrome is characterized by associative learning deficits, reduced risk of cancer, dendritic spine dysmorphogenesis, and facial dysmorphism. However, the molecular mechanism that links loss of function of FMR1 to the learning disability remains unclear. Here, we report an examination of small GTPase Ras signaling and synaptic AMPA receptor (AMPA-R) trafficking in cultured slices and intact brains of wild-type and FMR1 knock-out mice. In FMR1 knock-out mice, synaptic delivery of GluR1-, but not GluR2L- and GluR4-containing AMPA-Rs is impaired, resulting in a selective loss of GluR1-dependent long-term synaptic potentiation (LTP). Although Ras activity is upregulated, its downstream MEK (extracellular signal-regulated kinase kinase)-ERK (extracellular signal-regulated kinase) signaling appears normal, and phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB; or Akt) signaling is compromised in FMR1 knock-out mice. Enhancing Ras-PI3K-PKB signaling restores synaptic delivery of GluR1-containing AMPA-Rs and normal LTP in FMR1 knock-out mice. These results suggest aberrant Ras signaling as a novel mechanism for fragile X syndrome and indicate manipulating Ras-PI3K-PKB signaling to be a potentially effective approach for treating patients with fragile X syndrome.
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PMID:Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome. 1866 17