title: PAX6 3' deletion in a family with aniridia.
abstract: BACKGROUND
  Aniridia is a congenital panocular malformation defined as iris aplasia or hypoplasia. It can be either isolated or be a part of multiple ocular anomalies such as cataracts, glaucoma, corneal pannus, optic nerve hypoplasia, absence of macular reflex or ectopia lentis. In the majority of cases the disease is caused by mutation in the PAX6 gene.
  
  
  METHODS
  A Polish family with aniridia was screened for the presence of genomic rearrangements in PAX6, WT1 and the flanking genes by means of multiplex ligation probe amplification (MLPA). MLPA reaction was performed using the P219-B1 PAX6 commercial kit from MRC-Holland. Additionally, the coding sequence of PAX6 gene was sequenced in the proband. Array comparative genomic hybridization analysis was performed using the NimbleGen CGX-12 format.
  
  
  RESULTS
  MLPA examination revealed a heterozygous deletion of approximately 0.6  Mb, downstream of PAX6 gene on chromosome 11. Four genes lie in the deleted region. Bi-directional sequencing of 14 exons of the PAX6 gene did not reveal any causative alteration. Microarray analysis confirmed the deletion and determined its size which ranged from 598.87-651.76 kb.
  
  
  CONCLUSIONS
  A small subset of aniridia cases is caused by rearrangements of PAX6 neighboring regions, and the so-called "position effect" is considered to be the underlying pathogenic mechanism. Molecular testing of aniridia patients should include sequencing of the PAX6 gene, followed by screening for larger structural abnormalities located on chromosome 11p13. MLPA can be a useful method in molecular testing of aniridia patients.
authors: Department of Medical Genetics, Poznan University of Medical Science, Poznan, Poland. ania.wawrocka@gmail.com
authors: Anna
authors: A
authors: Wawrocka
authors: Bartlomiej
authors: B
authors: Budny
authors: Szymon
authors: S
authors: Debicki
authors: Aleksander
authors: A
authors: Jamsheer
authors: Anna
authors: A
authors: Sowinska
authors: Maciej Robert
authors: MR
authors: Krawczynski
mesh_terms: D024509:3' Flanking Region / Q000235:genetics*; D000328:Adult; D015783:Aniridia / Q000235:genetics*; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D014792:Visual Acuity / Q000502:physiology
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins