A new Peter's anomaly causative gene identified

Background and Aim: Anterior segment dysgenesis (ASD) includes a wide range of developmental disorders that affect Neural Crest Cells migration and differentiation into the cornea, iris, and lens. Peter's anomaly is an anterior segment dysgenesis disorder which causes blurred vision, and involves thinning and clouding of the cornea and attachment of the iris to the cornea. It may occur in isolation, or be a component of a broader syndrome. It is genetically heterogeneous, but most known causative genes have extracellular matrix functions or encode transcription factors. Disease occurrence is most often sporadic, but may evidence recessive or occasionally dominant inheritance. Screening studies suggest that all recognized causative genes have not yet been identified. Here, we aimed to identify the causative gene in a family with three affected membersMethods: The three Peter's anomaly affected patients and available family members were recruited, and DNA was isolated from peripheral blood cells. Whole exome sequencing was performed on the DNA of the patients, and sequence variations shared among the three patients were identified. Segregation analysis and screenings of candidate causative variations in control individuals were performed. In order to address involvement of the gene in eye development, its expression was quantified by Real Time PCR in various human embryonic and adult eye tissues.Results: Inheritance of disease in the family was ostensibly autosomal recessive. A homozygous mutation in a gene not previously associated with Peter's anomaly was the only shared variation among the patients. It segregated with disease status in the family and was absent in controls. Real Time PCR data showed that it is expressed in the cornea, iris, sclera, lens and retina of both human adults and embryos. The results tentatively suggest that its expression may be higher in embryonic iris and retina tissues.Conclusion: The identified gene encodes a member of a family of proteins involved in morphogenesis and cell differentiation. Its observed increased expression in some embryonic eye tissues requires confirmation in more embryos. Nevertheless, this finding, particularly higher expression in the iris, is consistent with having a role in the morphogenesis of the eye and involvement in Peter's anomaly pathogenesis.

Keywords:

Peter's anomaly , exome sequencing