Evidence against ZNF469 being causative for keratoconus in Polish patients

Justyna A. Karolak , Tomasz Gambin , Małgorzata Rydzanicz , Jacek Paweł Szaflik , Piotr Polakowski , Agata Frajdenberg , Małgorzata Mrugacz , Monika Podfigurna-Musielak , Paweł Stankiewicz , Marzena Gajecka


PURPOSE: 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.

CONCLUSION: 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.

Author Justyna A. Karolak - [Poznan University of Medical Sciences]
Justyna A. Karolak,,
, Tomasz Gambin (FEIT / IN)
Tomasz Gambin,,
- The Institute of Computer Science
, Małgorzata Rydzanicz - [Medical University of Warsaw]
Małgorzata Rydzanicz,,
, Jacek Paweł Szaflik - [Samodzielny Publiczny Kliniczny Szpital Okulistyczny]
Jacek Paweł Szaflik,,
, Piotr Polakowski - [Samodzielny Publiczny Kliniczny Szpital Okulistyczny]
Piotr Polakowski,,
, Agata Frajdenberg - [Linköpings universitet]
Agata Frajdenberg,,
, Małgorzata Mrugacz - [Uniwersytet Medyczny w Białymstoku]
Małgorzata Mrugacz,,
- Uniwersytet Medyczny w Białymstoku
, Monika Podfigurna-Musielak - [Medical Centre Vigor Med]
Monika Podfigurna-Musielak,,
, Paweł Stankiewicz - [Baylor College of Medicine]
Paweł Stankiewicz,,
, Marzena Gajecka - [Poznan University of Medical Sciences]
Marzena Gajecka,,
Journal seriesActa Ophthalmologica, ISSN 1755-375X
Issue year2016
Publication size in sheets0.5
Keywords in EnglishSanger sequencing; ZNF469; keratoconus; keratoconus genetics; whole-exome sequencing
ASJC Classification2731 Ophthalmology; 2700 General Medicine
URL https://www.ncbi.nlm.nih.gov/pubmed/26806788
ProjectDevelopment of new algorithms in the areas of software and computer architecture, artificial intelligence and information systems and computer graphics . Project leader: Rybiński Henryk, , Phone: +48 22 234 7731, start date 18-05-2015, end date 30-11-2016, II/2015/DS/1, Completed
WEiTI Działalność statutowa
Languageen angielski
Score (nominal)35
Score sourcejournalList
ScoreMinisterial score = 35.0, 27-08-2020, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 27-08-2020, ArticleFromJournal
Publication indicators WoS Citations = 11; Scopus Citations = 11; GS Citations = 17.0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.511; WoS Impact Factor: 2016 = 3.157 (2) - 2016=2.812 (5)
Citation count*18 (2020-08-30)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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