title: A novel PAX6 deletion in a Chinese family with congenital aniridia.
abstract: OBJECTIVE
  To identify a disease-causing paired box 6 (PAX6) gene mutation in a Chinese family affected by autosomal dominant congenital aniridia.
  
  
  METHODS
  All participants in the study, including the aniridia family and 100 unrelated senile cataract controls, received a comprehensive ophthalmic examination. Genomic DNA was extracted from their whole blood. Mutation screen in all exons and their adjacent splicing junctions of PAX6 was performed by direct sequencing of polymerase chain reaction (PCR) products. PCR products of heterozygous mutation were further cloned into T-vectors and confirmed by sequencing. Multiple alignments were performed using ClustalX to compare PAX6 protein sequences among vertebrates. MicroRNA binding sites were predicted by TargetScan.
  
  
  RESULTS
  A novel heterozygous PAX6 deletion c.1251_1353del103 (p.Pro418Serfs*87) affecting exon 14 and the 3'-untranslated-region (3'-UTR) was identified in the congenital aniridia family. The mutation was exclusively observed in all affected family members but not in any unaffected family member or unrelated control. Bioinformatics analysis showed that the deletion led to remarkable changes of the PAX6 protein, including a frameshift, changes of protein sequence, and a COOH-terminal extension. Multiple alignments showed that the affected region of PAX6 shared high sequence identity (100%) among its vertebrate orthologs. The COOH-terminal extension might also affect microRNA binding sites in the 3'-UTR as predicted by TargetScan.
  
  
  CONCLUSIONS
  In the current study we reported a novel PAX6 deletion resulting in an abnormal PAX6 COOH-terminal extension in the Chinese family affected by aniridia. Our findings thus add to the mutation spectrum of PAX6.
authors.affiliation: Joint Shantou International Eye Center, Shantou University & the Chinese University of Hong Kong, Shantou, China.
authors.forename: Jian Huan
authors.initials: JH
authors.lastname: Chen
authors.forename: Weitao
authors.initials: W
authors.lastname: Lin
authors.forename: Guoying
authors.initials: G
authors.lastname: Sun
authors.forename: Chukai
authors.initials: C
authors.lastname: Huang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Huang
authors.forename: Haoyu
authors.initials: H
authors.lastname: Chen
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015783:Aniridia / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D005136:Eye Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins