#1792 Phenotypic variability in PAX2-related nephropathies: a monocentric study

Abstract Background and Aims Pax2 mutations are known to cause kidney disease; both syndromic conditions, as kidney coloboma syndrome, and kidney specific disorders, as FSGS, have been described. Due to the rarity of Pax2-related nephropathies, data on genotype-phenotype correlation are limited. Method This observational and mono-centric study describes three families (A, G, P) referring to our Nephrology center, carrying Pax2 mutations. A total of 12 subjects were investigated: 2 individuals in family A, 4 in family G and 6 in the family P. Genetic analysis was carried out by NGS; detected mutations were confirmed by Sanger sequencing. Results Family A It includes 2 affected subjects, a 40 year-old woman and her mother (Fig. 1A). The mother had chorioretinic coloboma and was under hemodialytic therapy since the age of 50. The daughter had chorioretinic coloboma and bilateral renal hypodysplasia, proteinuria and a progressive decline of the eGFR since 34 years; renal biopsy excluded the presence of GN (Table 1). Both have the heterozygote c.890delC variant (p.Thr297fs) in Pax2. Family G It includes 4 affected individuals belonging to 3 different generations (Fig. 1B). The disorder was discovered after the evidence of advanced renal failure in a pregnant 27 y-old lady. The study of her family revealed the presence of kidney disease in her sister (transplanted on young age) and her father; one of her children has the mutation (Table 1). The PAX2 c.194T>C(p.Val65Ala HET) mutation segregates with the phenotype in the family. Family P It includes 6 affected individuals of 3 different generations (Fig. 1C); the index-case presented with heavy proteinuria: kidney biopsy revealed a C3 nephropathy. His son was transplanted when 18 years old for bilateral renal hypoplasia. His mother died after some years of dialysis (Table 1). PAX2 mutation on exon3: c.361G>A(p.Glu121Lys HET). Conclusion This case series demonstrates the phenotypic variability of patients with Pax2 mutations and suggests the utility of new generation genetics (NGS) to get the diagnosis in atypical conditions. The implementation of international registers and basic studies will be indispensable to define the mechanisms involved in the development of the disease and to address the reasons of clinical variability.