PAX6 mutations: genotype-phenotype correlations
Φόρτωση...
Ημερομηνία
Συγγραφείς
Tzoulaki, I.
White, I. M.
Hanson, I. M.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
BMC Genet
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
BACKGROUND: The PAX6 protein is a highly conserved transcriptional regulator that is important for normal ocular and neural development. In humans, heterozygous mutations of the PAX6 gene cause aniridia (absence of the iris) and related developmental eye diseases. PAX6 mutations are archived in the Human PAX6 Allelic Variant Database, which currently contains 309 records, 286 of which are mutations in patients with eye malformations. RESULTS: We examined the records in the Human PAX6 Allelic Variant Database and documented the frequency of different mutation types, the phenotypes associated with different mutation types, the contribution of CpG transitions to the PAX6 mutation spectrum, and the distribution of chain-terminating mutations in the open reading frame. Mutations that introduce a premature termination codon into the open reading frame are predominantly associated with aniridia; in contrast, non-aniridia phenotypes are typically associated with missense mutations. Four CpG dinucleotides in exons 8, 9, 10 and 11 are major mutation hotspots, and transitions at these CpG's account for over half of all nonsense mutations in the database. Truncating mutations are distributed throughout the PAX6 coding region, except for the last half of exon 12 and the coding part of exon 13, where they are completely absent. The absence of truncating mutations in the 3' part of the coding region is statistically significant and is consistent with the idea that nonsense-mediated decay acts on PAX6 mutant alleles. CONCLUSION: The PAX6 Allelic Variant Database is a valuable resource for studying genotype-phenotype correlations. The consistent association of truncating mutations with the aniridia phenotype, and the distribution of truncating mutations in the PAX6 open reading frame, suggests that nonsense-mediated decay acts on PAX6 mutant alleles.
Περιγραφή
Λέξεις-κλειδιά
Alleles, Aniridia/genetics, Codon, Nonsense, Databases, Nucleic Acid, Eye Abnormalities/*genetics, Eye Proteins/*genetics, Genotype, Homeodomain Proteins/*genetics, Humans, *Mutation, Open Reading Frames/genetics, Paired Box Transcription Factors/*genetics, Phenotype, Repressor Proteins/*genetics
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/15918896
http://www.biomedcentral.com/1471-2156/6/27
http://www.biomedcentral.com/1471-2156/6/27
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής