Renal hypoplasia without optic coloboma associated with PAX2 gene deletion

PAX2 gene encodes a transcription factor that belongs to the paired-box family of homeotic genes and is widely expressed during the development of both ductal and mesenchymal components of the urogenital system. Human PAX2 gene maps on chromosome 10q24-q25 and comprises 12 exons. Exons 1–4 encode the paired box domain, which is essential for DNA-binding activity. At early stages, the gene is expressed in neural tube cells. Later on, its expression is detected in the developing urogenital system as well as in the ear, eye and central nervous system (CNS). In the urogenital system, PAX2 is expressed in the induced nephrogenic mesenchyme, during the mesenchymal-to-epithelial transition that preludes to glomerulus formation. Its expression is also detected in the branching ureteric bud, in collecting duct epithelia and in uterus, oviduct, vas deferent and epidydimis. PAX2 is thought to orchestrate the pattern of gene expression, including that of other PAX family members, also during other organ development. In humans, PAX2 heterozygous mutations, arising de novo or inherited in an autosomal dominant fashion, have been associated with renal coloboma syndrome (RCS) (OMIM 120330). Phenotypic features of the syndrome have been related to PAX2 haploinsufficiency. Haploinsufficiency deals with the notion that level of protein is critical to its correct function. RCS hallmarks are bilateral optic nerve coloboma and renal hypoplasia. The term coloboma includes developmental abnormalities of the optic nerve (ranging from mild optic disc dysplasia to optic nerve aplasia), retina, choroid and iris [1]. Renal hypoplasia is the most common renal abnormality (60% of patients). Oligomeganephronia, renal dysplasia or multicystic dysplastic kidney have also been reported [2–4]. Additional congenital anomalies may …