title: Molecular Screening of Keratoconus Susceptibility Sequence Variants in VSX1, TGFBI, DOCK9, STK24, and IPO5 Genes in Polish Patients and Novel TGFBI Variant Identification.
abstract: OBJECTIVE
  Keratoconus (KTCN) is a degenerative disorder of the eye that results in the conical shape and thinning of the cornea and is a leading cause for corneal transplantations. A number of studies suggest that genetic factors play a role in KTCN etiology. Some candidate gene variants have recently been shown to be associated with KTCN. The purpose of our study was to verify the role of VSX1, TGFBI, DOCK9, IPO5, and STK24 sequence variants in Polish KTCN patients.
  
  
  METHODS
  Forty-two Polish patients with sporadic KTCN and 50 control individuals were enrolled into this study. Both affected and unaffected individuals underwent detailed ophthalmic examination. The mutations screening in the candidate genes was performed by the direct sequencing method.
  
  
  RESULTS
  Analysis of VSX1, TGFBI, DOCK9, IPO5, and STK24 genes identified numerous sequence variants. Variants c.-264_-255delGGGGTGGGGT, c.627 + 23G > A, c.809-6_809-5insT, and c.*200G > T in the VSX1 gene, and heterozygous c.1598G > A mutation (Arg533Gln) in exon 12 of TGFBI were detected for the first time in KTCN patients. Two known sequence variants of TGFBI c.1620T > C (Phe540Phe) and c.1678 + 23G > A were observed in KTCN patients and control individuals. The newly reported c.717 + 43A > G substitution in intron 7 of DOCK9 was identified in both KTCN patients and healthy individuals.
  
  
  CONCLUSIONS
  Our investigation showed that KTCN-related sequence variants of analyzed genes were found in a very small proportion of the studied patients indicating that genes other than VSX1, TGFBI, DOCK9, IPO5, and STK24 are involved in the development and progression of KTCN in Polish patients. Our results support the hypothesis about the genetic heterogeneity of KTCN.
authors.affiliation: a Department of Genetics and Pharmaceutical Microbiology , Poznan University of Medical Sciences , Poznan , Poland .|b Institute of Human Genetics, Polish Academy of Sciences , Poznan , Poland , and.
authors.forename: Justyna A
authors.initials: JA
authors.lastname: Karolak
authors.affiliation: c Department of Ophthalmology , Medical University of Warsaw, SPKSO University Ophthalmic Hospital , Warsaw , Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Polakowski
authors.affiliation: c Department of Ophthalmology , Medical University of Warsaw, SPKSO University Ophthalmic Hospital , Warsaw , Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.affiliation: c 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: b Institute of Human Genetics, Polish Academy of Sciences , Poznan , Poland , and.
authors.forename: Marzena
authors.initials: M
authors.lastname: Gajecka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D056914:Genomic Structural Variation / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011044:Poland; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D055815:Young Adult; D028961:beta Karyopherins / Q000235:genetics; D000099222:betaIG-H3 Protein; D000099317:Hippo Kinases
chemical_list: D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D017346:Protein Serine-Threonine Kinases; D016212:Transforming Growth Factor beta; D028961:beta Karyopherins; D000099222:betaIG-H3 Protein; C466321:DOCK9 protein, human; C107940:IPO5 protein, human; C491583:VSX1 protein, human; C109163:STK24 protein, human; D000099317:Hippo Kinases
keywords: Candidate genes; TGFBI; VSX1; keratoconus; molecular screening