Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a report on the nature of the mutations in the PAX6 gene in twenty patients with aniridia. Five of the twenty patients had sporadic aniridia with deletions in chromosome 11p13. Three of the five had WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, mental retardation), and the other two had deletions whose breakpoints occurred between the PAX6 and the WT1 genes. Allelic losses at PAX6 were of paternal origin. The remaining fifteen patients with aniridia had intragenic mutations in the PAX6 gene, with mutations found from exon 5 to exon 12. Twelve cases of dysfunctional PAX6 were due to premature termination of the protein by nonsense mutations (five cases), splicing defect (one case), deletion (two cases), deletion-insertions (two cases), and tandem repeat insertions (two cases). One patient (P2) had a PAX6 protein with de novo in-frame deletion of alanine, arginine, and proline at codon positions 37, 38, and 39. These codons are in the paired box region, and codon 38 is in contact with the phosphate group of the sugar-phosphate backbone of the target DNA. Another patient (P8) had a single nucleotide transition at c.1182 (nucleotide number, Genbank accession #M93650, used as in Glaser et al. [1992]), which generated both a missense mutation (Q255H) and a splicing defect. A missense mutation was found at G387E in a third patient (P10). All observed mutations support the notion that haploinsufficiency in PAX6 results in aniridia and associated eye anomalies.
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PMID:Mutation in the PAX6 gene in twenty patients with aniridia. 1073 78

We have identified nine novel intragenic mutations of the PAX6 gene in 30 patients with aniridia. One patient with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR syndrome) had deletion of 11p and had lost the paternal PAX6 allele. Two patients had small deletions: a frameshift that should result in early termination of the PAX6 protein, and a frameshift that leads to a termination-site change and run-on into the 3' untranslated region (UTR). The other 27 patients had single base-pair mutations. Four had splicing defects; three had IVS6+1G>A, which was at a mutation hotspot in the PAX6 gene; 10 had premature termination (four 1024C>T [R203X], also at a mutation hotspot); and six had missense mutations. Missense mutation A321T (1378G>A) was a polymorphic change; the other five missense mutations were L46R, C52R, I56T, G73D, and I87K. These five codons are in the PAX6 paired domain and are highly conserved throughout the entire paired family. Seven patients had a mutation in the normal stop codon (TAA). This change leads to run-on into the 3' UTR and is also at a mutation hotspot. All 30 mutations should result in PAX6 haploinsufficiency. No correlation was observed between mutation sites and phenotypes.
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PMID:Missense mutations in the DNA-binding region and termination codon in PAX6. 1255 61