title: A large novel deletion downstream of PAX6 gene in a Chinese family with ocular coloboma.
abstract: OBJECTIVE
  The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial ocular coloboma in a large Chinese family.
  
  
  METHODS
  After linkage analysis was carried out in this family, all exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. Then the genome of the proband was evaluated by a microarray-based comparative genomic hybridization (aCGH). Quantitative real-time PCR was applied to verify the abnormal aCGH findings.
  
  
  RESULTS
  All patients presented bilateral partial coloboma of iris, severe congenital nystagmus, hyperpresbyopia and congenital posterior polar cataracts. Two-point linkage analysis in the autosomal dominant family showed loss of heterozygosity at the D11S914 locus. There was no pathogenic mutation in the exons of PAX6. The aCGH analysis revealed a 681 kb heterozygous deletion on chromosome 11p13. Quantitative real-time PCR verified the deletion in the patients and further confirmed this deletion cosegregation with the ocular coloboma phenotype in the family.
  
  
  CONCLUSIONS
  The 681 kb large deletion of chromosome 11p13 downstream of PAX6 is the genetic cause of the familial ocular coloboma in this large Chinese family. aCGH should be applied if there is a negative result for the mutation detection of PAX6 in patients with ocular coloboma.
authors.affiliation: Department of Medical Genetics, Third Military Medical University, Shapingba District, Chongqing, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Medical Genetics, Third Military Medical University, Shapingba District, Chongqing, PR China.
authors.forename: Limeng
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Ophthalmology, Xinqiao Hospital, Third Military Medical University, Shapingba District, Chongqing, PR China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Xinqiao Hospital, Third Military Medical University, Shapingba District, Chongqing, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Medical Genetics, Third Military Medical University, Shapingba District, Chongqing, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D001483:Base Sequence; D002681:China; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D003103:Coloboma / Q000235:genetics* / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins