title: A recurrent PAX6 mutation is associated with aniridia and congenital progressive cataract in a Chinese family.
abstract: OBJECTIVE
  Aniridia is phenotyically and genetically heterogeneous. This study is to summarize the phenotypes and identify the genetic defect responsible for aniridia and congenital progressive cataract in a three generation Chinese family.
  
  
  METHODS
  A detailed family history and clinical data from patients were collected by ophthalmologic examination, including visual acuity, slit-lamp examination, tonometer, keratometry, corneal topography, optical coherence tomography, and ultrasonic A/B scan. All exons and flanking intronic sequences of the paired box 6 (PAX6) gene were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structure and function of the mutant PAX6 were analyzed by bioinformatics analysis.
  
  
  RESULTS
  All the six patients shared common manifestations of complete aniridia, congenital cataract and thickened cornea, and broad phenotypic variability was observed in nystagmus, ptosis, strabismus, glaucoma, corneal pannus, corneal curvature, corneal vascularization, cataract subtype, ectopia lentis, axial length, and optic disc anomalies. Sequencing of the candidate gene detected a heterozygous c.307C>T transition in the coding region of PAX6, resulting in the substitution of a highly conserved arginine codon for a termination codon (p.R103X). The p.P103X mutation co-segregated with the affected individuals in the family. The change was supposed to cause structural and functional changes based on computational analysis.
  
  
  CONCLUSIONS
  We identified a recurrent PAX6 c.307C>T mutation in an aniridia and congenital progressive cataract family, and summarized the variable phenotypes among the patients, which expanded the phenotypic spectrum of aniridia in a different ethnic background.
authors.affiliation: Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.
authors.forename: Chongfei
authors.initials: C
authors.lastname: Jin
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Wang
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xingchao
authors.initials: X
authors.lastname: Shentu
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
mesh_terms: D000328:Adult; D015783:Aniridia / Q000150:complications / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000150:complications / Q000151:congenital / Q000235:genetics*; D002648:Child; D018450:Disease Progression; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins