title: Evidence against ZNF469 being causative for keratoconus in Polish patients.
abstract: OBJECTIVE
  Keratoconus (KTCN) is a degenerative disorder characterized by stromal thinning and protrusion of the cornea, resulting in severe impairment of visual function. A recent study proposed that rare heterozygous mutations in ZNF469 determine KTCN aetiology.
  
  
  METHODS
  To investigate the contribution of ZNF469 to KTCN, we Sanger sequenced ZNF469 in 42 unrelated Polish patients with KTCN and 49 Polish individuals with high myopia (HM) and compared the results with whole-exome sequencing (WES) data performed in 268 Polish individuals without ocular abnormalities.
  
  
  RESULTS
  The average number of ZNF469 non-synonymous variants was 16.31 and 16.0 for individuals with KTCN and HM, respectively (p = 0.3724). All identified variants were previously reported. Alternative allele frequency (AAF) was determined based on the WES results. Among missense variants, only one (rs528085780) has AAF ≤ 0.001 and was identified in one patient with sporadic KTCN. However, the resulting Arg1864Lys substitution was not predicted to be deleterious.
  
  
  CONCLUSIONS
  In summary, we have not found a significant enrichment of sequence variants in ZNF469 in Polish patients with KTCN. High prevalence of ZNF469 variants identified in our KTCN group is typical for a common genetic variation observed in general population. Our findings indicate that variation in ZNF469 is not responsible for KTCN and other genetic variants are involved in the development and progression of this disease in Polish patients.
authors.affiliation: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Justyna A
authors.initials: JA
authors.lastname: Karolak
authors.affiliation: Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland.|Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO University Ophthalmic Hospital, Warsaw, Poland.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, SPKSO University Ophthalmic Hospital, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Polakowski
authors.affiliation: Department of Ophthalmology, Linköping University, Linköping, Sweden.
authors.forename: Agata
authors.initials: A
authors.lastname: Frajdenberg
authors.affiliation: Department of Ophthalmology and Eye Rehabilitation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Mrugacz
authors.affiliation: Medical Centre Vigor Med, Leszno, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Podfigurna-Musielak
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.affiliation: Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Gajecka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011044:Poland; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D014157:Transcription Factors; C530065:ZNF469 protein, human
keywords: Sanger sequencing; ZNF469; keratoconus; keratoconus genetics; whole-exome sequencing