OBJECTIVES: Keratoconus (KC) is a progressive corneal ectasia disorder, arising from a myriad of causes including genetic predispositions, environmental factors, biomechanical influences, and inflammatory reactions. This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population. METHODS: Twenty-five patients with primary KC as well as 50 unrelated population-matched healthy controls, were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population. Sanger sequencing and whole-exome sequencing (WES) were used to analyze mutations in the zinc finger protein 469 (ZNF469) gene. Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis. RESULTS: Five novel heterozygous missense variants were identified in KC patients. Among them, 2 compound heterozygous variants, c.8986G>C (p. E2996Q) with c.11765A>C (p. D3922A), and c.4423C>G (p. L1475V) with c.10633G>A (p. G3545R), were determined to be possible pathogenic factors for KC. CONCLUSIONS Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population. These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
Adolescent ; Adult ; Female ; Humans ; Male ; Case-Control Studies ; China/ethnology* ; Exome Sequencing ; Genetic Predisposition to Disease ; Keratoconus/genetics* ; Mutation ; Mutation, Missense ; Transcription Factors/genetics* ; East Asian People/genetics*

OBJECTIVETo investigate the point mutations and polymorphisms of transforming growth factor beta-induced gene (TGFBI) in Chinese patients with keratoconus and discuss the relationship between the feature of gene mutations and single nucleotide polymorphisms of TGFBI gene and keratoconus.

METHODSPolymerase chain reaction single strand conformation polymorphism and DNA direct sequencing were performed in 30 keratoconus cases and 30 healthy controls. All 17 exons of the TGFBI gene were analyzed for point mutations and single nucleotide polymorphisms.

RESULTSTotally two heterozygous nucleotide changes were identified in exon 12 of the TGFBI gene. The codon 535 is changed from GGA to TGA in 1 patient, leading to a substitution of glycine to a stop codon at the protein level (G535X). The codon 540 is changed from TTT to TTC in 2 patients and 1 control individual, resulting in a nonsense mutation (F54F), and is a single nucleotide polymorphism of the gene.

CONCLUSIONMutation and polymorphisms of the TGFBI gene were detected in Chinese patients with keratoconus in this study. The results suggest that TGFBI gene might play an important role in the pathogenesis of keratoconus.

Adolescent ; Adult ; Case-Control Studies ; Child ; China ; Extracellular Matrix Proteins ; genetics ; Female ; Glycine ; deficiency ; genetics ; Humans ; Keratoconus ; genetics ; Male ; Middle Aged ; Point Mutation ; Polymerase Chain Reaction ; methods ; Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational ; Sequence Analysis, DNA ; methods ; Transforming Growth Factor beta ; genetics ; Young Adult

OBJECTIVESTo observe the expression of betaig-h3 in normal cornea and keratoconus and to elucidate the role of extracellular matrix in keratoconus.

METHODSIn situ hybridization was used to detect the expression of betaig-h3 in the cornea. The cDNA library was screened with human betaig-h3 cDNA probe to locate betaig-h3 mRNA in cells.

RESULTSExpression of betaig-h3 was found mainly in the stroma of the normal cornea and keratoconus, but decrease depending on the degree of keratopathy. In some serious cases, no expression signal was detected. The strongest expression was seen at the border of the normal region and keratoconus.

CONCLUSIONSbetaig-h3, the structural component of the extracellular matrix, can affect cell adhensiveness in the development of corneal fibrous interstitial organization. During the development of keratoconus, decreasing levels of betaig-h3 cause the diminution of corneal steadiness, which is related to formation of keratoconus.

Cornea ; metabolism ; Extracellular Matrix Proteins ; Humans ; Keratoconus ; metabolism ; Neoplasm Proteins ; genetics ; RNA, Messenger ; analysis ; Transforming Growth Factor beta ; Wound Healing