Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In abused children cerebral contusion can lead to neurologic sequelae or mental retardation. Cerebral injury has been found with and without external evidence of head injury. We report the sonographic findings in a case of battered-child syndrome. Cerebral sonography could demonstrate cerebral contusion at the time of admission. On repeated examination white matter clefts developed in both frontal lobes. The sonographic findings were confirmed by CCT.
 ...
PMID:Sonographic demonstration of contusional white matter clefts in an infant. 673 17

The transcriptional silencing of the human gene, fragile X mental retardation 1 (FMR1), is due to abnormal methylation in response to an expanded 5'-untranslated CGG trinucleotide repeat and accounts for most cases of fragile X syndrome, a frequent inherited form of mental retardation. Although the encoded fragile X mental retardation protein (FMRP) is known to have properties of a RNA-binding protein, the precise function of FMRP remains to be elucidated. We report the cloning of the chicken homolog of FMR1 and show strong evolutionary conservation, with nucleotide and amino acid identities of 85 and 92%, respectively, between chicken and human. In place of the mammalian CGG trinucleotide repeat, a 99-nt tripartite repetitive element containing a CCT trinucleotide repeat flanked on both sides by dinucleotide repeats was identified. Blocks of highly conserved 3'-untranslated sequence were also found. Within the coding region, two copies each of the highly conserved K homology motif and the Arg-Gly-Gly (RGG) box motif, both ribonucleotide particle family domains implicated in RNA binding, were identified. Chicken FMRP was found to bind RNA in vitro, and this activity correlated with the presence of the carboxy-terminal portion of the protein that includes the RGG motifs.
 ...
PMID:The chicken FMR1 gene is highly conserved with a CCT 5'-untranslated repeat and encodes an RNA-binding protein. 880 73

Microtubules are indispensable dynamic structures that contribute to many essential biological functions. Assembly of the native alpha/beta tubulin heterodimer, the subunit that polymerizes to form microtubules, requires the participation of several molecular chaperones, namely prefoldin, the cytosolic chaperonin CCT, and a series of five tubulin-specific chaperones termed cofactors A-E (TBCA-E). Among these, TBCC, TBCD, and TBCE are essential in higher eukaryotes; they function together as a multimolecular machine that assembles quasinative CCT-generated alpha- and beta-tubulin polypeptides into new heterodimers. Deletion and truncation mutations in the gene encoding TBCE have been shown to cause the rare autosomal recessive syndrome known as HRD, a devastating disorder characterized by congenital hypoparathyroidism, mental retardation, facial dysmorphism, and extreme growth failure. Here we identify cryptic translational initiation at each of three out-of-frame AUG codons upstream of the genetic lesion as a unique mechanism that rescues a mutant HRD allele by producing a functional TBCE protein. Our data explain how afflicted individuals, who would otherwise lack the capacity to make functional TBCE, can survive and point to a limiting capacity to fold tubulin heterodimers de novo as a contributing factor to disease pathogenesis.
 ...
PMID:Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD. 1693 82

The trinucleotide repeat sequence CGG/CCG is known to expand in the human genome. This expansion is the primary pathogenic signature of fragile X syndrome, which is the most common form of inherited mental retardation. It has been proposed that formation of non-B conformations by the repetitive sequence contributes to the expansion mechanism. It is also known that the CGG/CCG repeat sequence of healthy individuals, which is not prone to expansion, contains AGG/CCT interruptions every 8-11 CGG/CCG repeats. Using DNA containing 19 or 39 CGG repeats, we have found that both the position and number of interruptions modulate the non-B conformation adopted by the repeat sequence. Analysis by chemical probes revealed larger loops and the presence of bulges for sequences containing interruptions. Additionally, using optical analysis and calorimetry, the effect of these structural changes on the thermodynamic stability of the conformation has been quantified. Notably, changing even one nucleotide, as occurs when CGG is replaced with an AGG interruption, causes a measurable decrease in the stability of the conformation adopted by the repeat sequence. These results provide insight into the role interruptions may play in preventing expansion in vivo and also contribute to our understanding of the relationship between non-B conformations and trinucleotide repeat expansion.
 ...
PMID:AGG interruptions in (CGG)(n) DNA repeat tracts modulate the structure and thermodynamics of non-B conformations in vitro. 2069 23