Abstract: Objective To analyze the clinical phenotype of and pathogenic gene mutation in a male child with keratoconus, to identify the mutation site of the pathogenic gene, and to discuss the relationship between genotype and phenotype. Methods Clinical data of a male child with keratoconus and his parents were collected. Pentacam corneal topography, Belin/Ambrosio Enhanced Ectasia Display, and biomechanical analysis were used to improve the diagnosis of keratoconus. Peripheral blood genomic DNA of the family members was obtained, and the exome of the proband was sequenced using whole exome sequencing technology. Finally, the pathogenic mutation was found to be co-segregated within the family, and the relationship between the mutation and patient phenotype was further analyzed. Results The proband and his father were both diagnosed with keratoconus. Whole exome sequencing revealed a mutation(c.643G>C)in the zinc finger E-box-binding homeobox 1(ZEB1)gene that led to replacement of valine at 215 position in the protein encoded by ZEB1 with leucine(p.V215L). Conservative analysis showed that this mutation is highly conserved in various species. Bioinformatics predictions showed that the mutation is highly pathogenic. Mutations in the gene were also present in the paternal gene. The mother of the proband presented with normal clinical manifestations, and the mutation was not detected in the genetic tests of the mother and 100 unrelated normal controls. Conclusions The clinical phenotypes of both proband and his father were consistent with the typical keratoconus phenotype. Exon sequencing revealed a new mutation in the ZEB1 gene(c.643G>C, p.V215L). The mutation was co-segregated within the family.

Key words: Keratoconus, Whole exome sequencing, ZEB1, Biomechanical analysis, Pentacam system