A novel variant affecting the cytoplasmic tail of the FAT1 protocadherin causing coloboma and renal failure: A case report.

Background: Variations in the protocadherin gene have recently been associated with a syndrome that includes coloboma, facial dysmorphism, renal failure, syndactyly, and other developmental defects.

Materials And Methods: Detailed medical and family history, physical examination, and molecular analysis.

Results: This non-dysmorphic, intellectually normal 51-year-old woman presented with bilateral colobomata and renal failure of unclear etiology, and asymmetric sensorineural hearing loss. Family history was notable for multiple family members with various forms of cancer. Whole exome sequencing revealed a homozygous frame shift variant in , predicted to truncate the FAT1 protein at the furthest position in the protein structure published to date in a patient with coloboma.

Conclusions: This case provides further evidence of the pleiotropic effects of FAT1 in optic fissure closure and kidney function. Also, because this variant is in the last exon, it would be anticipated to escape nonsense-mediated decay, opening the possibility that the protein is made and expressed, but not completely functional, as its intracellular domain is truncated.