We did discover a significant association of 627+23G>A polymorphism distribution (VSX1) with unrelated patients diagnosed with the hereditary form of KC.
A total of 66 unrelated patients with keratoconus from the European population (27 with familial keratoconus; 39 with sporadic keratoconus) were analysed for VSX1 mutations.
DNA extraction, PCR amplification, and direct sequencing of the VSX1 gene were performed in 100 unrelated patients with diagnoses of clinical and topographic features of KTCN.
Family-based studies have recently led to the identification of the MIR184 gene for keratoconus with cataract and to the DOCK9 gene in a family with isolated keratoconus.
We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract by deep sequencing of a linkage region known to contain the mutation.
Recently, polymorphisms in the seed region of miR-184 have been identified in familial severe KC and stromal thinning (endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning [EDICT]) syndrome.
The following six single-nucleotide polymorphisms (SNPs) that showed a statistically significant association with KC in a recent GWAS study were selected for genotyping in our cohort: rs4894535 (FNDC3B), rs1324183 (MPDZ-NF1B), rs1536482 (RXRA-COL5A1), rs7044529 (COL5A), rs2721051 (FOXO1), and rs9938149 (BANP-ZNF469).
We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)).
The following six single-nucleotide polymorphisms (SNPs) that showed a statistically significant association with KC in a recent GWAS study were selected for genotyping in our cohort: rs4894535 (FNDC3B), rs1324183 (MPDZ-NF1B), rs1536482 (RXRA-COL5A1), rs7044529 (COL5A), rs2721051 (FOXO1), and rs9938149 (BANP-ZNF469).
We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)).
The aim of the current study was to investigate the frequency of ZNF 469 gene variants in rapidly progressive advance keratoconus patients who underwent corneal transplant surgery by the age of 30, compared to their frequency in the normal Turkish population.
This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.
Four carriers of three BCS1-associated ZNF469 loss-of-function mutations (p.[Glu1392Ter], p.[Gln1930Argfs*6], p.[Gln1930fs*133]) were examined and none had keratoconus.