title: Assessment of PAX6 alleles in 66 families with aniridia.
abstract: We report on PAX6 alleles associated with a clinical diagnosis of classical aniridia in 81 affected individuals representing 66 families. Allelic variants expected to affect PAX6 function were identified in 61 families (76 individuals). Ten cases of sporadic aniridia (10 families) had complete (8 cases) or partial (2 cases) deletion of the PAX6 gene. Sequence changes that introduced a premature termination codon into the open reading frame of PAX6 occurred in 47 families (62 individuals). Three individuals with sporadic aniridia (three families) had sequence changes (one deletion, two run-on mutations) expected to result in a C-terminal extension. An intronic deletion of unknown functional significance was detected in one case of sporadic aniridia (one family), but not in unaffected relatives. Within these 61 families, single nucleotide substitutions accounted for 30/61 (49%), indels for 23/61 (38%), and complete deletion of the PAX6 locus for 8/61 (13%). In five cases of sporadic aniridia (five families), no disease-causing mutation in the coding region was detected. In total, 23 unique variants were identified that have not been reported in the Leiden Open Variation Database (LOVD) database. Within the group assessed, 92% had sequence changes expected to reduce PAX6 function, confirming the primacy of PAX6 haploinsufficiency as causal for aniridia.
authors.affiliation: Neuroscience Division of the Biomedical and Health Sciences Institute, The University of Georgia, Athens, GA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Bobilev
authors.affiliation: Department of Cellular Biology, The University of Georgia, Athens, GA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: McDougal
authors.affiliation: Molecular Resource Center, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Taylor
authors.affiliation: Department of Ophthalmology in the Hamilton Eye Institute, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Geisert
authors.affiliation: Molecular Resource Center, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Netland
authors.affiliation: Neuroscience Division of the Biomedical and Health Sciences Institute, The University of Georgia, Athens, GA, USA.|Department of Cellular Biology, The University of Georgia, Athens, GA, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Lauderdale
mesh_terms: D000483:Alleles; D015783:Aniridia / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008958:Models, Molecular; D016254:Mutagenesis, Insertional; D009154:Mutation; D000071841:PAX6 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D017354:Point Mutation; D000072417:Protein Domains; D017384:Sequence Deletion
chemical_list: D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human
keywords: absent iris; chromosome 11p13; eye abnormalities; eye disease; irideremia