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

Deletion of chromosome 11p13 in humans produces the WAGR syndrome, consisting of aniridia (an absence or malformation of the iris), Wilms tumor (nephroblastoma), genitourinary malformations, and mental retardation. An interspecies backcross between Mus musculus/domesticus and Mus spretus was made in order to map the homologous chromosomal region in the mouse genome and to define an animal model of this syndrome. Nine evolutionarily conserved DNA clones from proximal human 11p were localized on mouse chromosome 2 near Small-eyes (Sey), a semidominant mutation that is phenotypically similar to aniridia. Analysis of Dickie's Small-eye (SeyDey), a poorly viable allele that has pleiotropic effects, revealed the deletion of three clones, f3, f8, and k13, which encompass the aniridia (AN2) and Wilms tumor susceptibility genes in man. Unlike their human counterparts, SeyDey/+ mice do not develop nephroblastomas. These findings suggest that the Small-eye defect is genetically equivalent to human aniridia, but that loss of the murine homolog of the Wilms tumor gene is not sufficient for tumor initiation. A comparison among Sey alleles suggests that the AN2 gene product is required for induction of the lens and nasal placodes.
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PMID:A mouse model of the aniridia-Wilms tumor deletion syndrome. 217 41

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by marked variation in clinical severity. To investigate the contribution to variability by genes either contiguous to or contained within the NF1 gene, we screened six NF1 patients with mild facial dysmorphology, mental retardation, and/or learning disabilities, for DNA rearrangement of the NF1 region. Five of the six patients had NF1 gene deletions on the basis of quantitative densitometry, locus hemizygosity, and analysis of somatic cell hybrid lines. Analyses of hybrid lines carrying each of the patient's chromosomes 17, with 15 regional DNA markers, demonstrated that each of the five patients carried a deletion > 700 kb in size. Minimally, each of the deletions involved the entire 350-kb NF1 gene; the three genes--EVI2A, EVI2B, and OMG--that are contained within an NF1 intron; and considerable flanking DNA. For four of the patients, the deletions mapped to the same interval; the deletion in the fifth patient was larger, extending farther in both directions. The remaining NF1 allele presumably produced functional neurofibromin; no gene rearrangements were detected, and RNA-PCR demonstrated that it was transcribed. These data provide compelling evidence that the NF1 disorder results from haploid insufficiency of neurofibromin. Of the three documented de novo deletion cases, two involved the paternal NF1 allele and one the maternal allele. The parental origin of the single remaining expressed NF1 allele had no dramatic effect on patient phenotype. The deletion patients exhibited a variable number of physical anomalies that were not correlated with the extent of their deletion. All five patients with deletions were remarkable for exhibiting a large number of neurofibromas for their age, suggesting that deletion of an unknown gene in the NF1 region may affect tumor initiation or development.
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PMID:Deletions spanning the neurofibromatosis 1 gene: identification and phenotype of five patients. 811 12

Gliomas are a heterogeneous group of tumors with evolving classification based on genotype. Isocitrate dehydrogenase (IDH) mutation is an early event in the formation of some diffuse gliomas, and is the best understood mechanism of their epigenetic dysregulation. Glioblastoma may evolve from lower-grade lesions with IDH mutations, or arise independently from copy number changes in platelet-derived growth factor receptor alpha (PDGFRA) and phosphatase and tensin homolog (PTEN). Several molecular subtypes of glioblastoma arise from a common proneural precursor with a tendency toward transition to a mesenchymal subtype. Following oncogenic transformation, gliomas escape growth arrest through a distinct step of aberrant telomere reverse transcriptase (TERT) expression, or mutations in either alpha thalassemia/mental retardation syndrome (ATRX) or death-domain associated protein (DAXX) genes. Metabolic reprogramming allows gliomas to thrive in harsh microenvironments such as hypoxia, acidity, and nutrient depletion, which contribute to tumor initiation, maintenance, and treatment resistance.
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PMID:Brain Tumors of Glial Origin. 3176 Jun 51