Phenotype and genotype features of isolated cystic kidney diseases with autosomal recessive type of inheritance in children

Abstract

   The relevance of the problem of hereditary cystic kidney diseases (cystosis) is due to the wide variability of the renal phenotype and the genotype that determines the prognosis, the progression to renal failure as early as in childhood.   Purpose. To present the results of the analysis of the correlation of genotype and phenotype, renal function in isolated cystic kidney diseases with an autosomal recessive type of inheritance in children.   Material and methods. in 14 children (from 13 families) aged 9 months — 17 years, the features of the clinical phenotype of kidney cysts with autosomal recessive type of inheritance and gene mutation were evaluated according to the results of a molecular genetic study.   Results. In 3 (23 %) of 13 families, the family history is burdened by kidney cysts. The characteristic of gene mutation in cystic kidney diseases with autosomal recessive type of inheritance in 13 patients is presented (in 2 tables). Of the 21 identified variants in the genes PKHD1, INVS, NPHP1, TMEM67, 15 (71 %) had known pathogenic significance, 6 (29 %) had previously undescribed variants in data-bases. Variants of the PKHD1 gene were identified in 11 children with the phenotype of polycystic kidney disease with autosomal recessive type of inheritance and liver fibrosis. In the study, variant C.107C>T (Thr36Met) is the most common among children with identified variants of the PKHD1 gene in autosomal recessive polycystic kidney disease in 5 out of 21 (23.8 %), c.664A>G (Ile222Val) in 1 (4.8 %), c.6992T>A (Ile2331Lys) in 1 (4.8 %), c.10444C>T (Arg3482Cys) at 1 (4.8 %). Infantile (n=1) and juvenile (n = 2) nephronophthysis were confirmed in 3 children with homozygous and compound heterozygous pathogenic variants in the INVS, NPHP1, TMEM67 genes.   Conclusion. The features of the genotype and phenotype are presented in 14 children with autosomal recessive type of inheritance of isolated kidney cysts in autosomal recessive polycystic kidney disease (n = 11) and nephronophthysis (n = 3), of whom chronic kidney disease was established in 13 children aged 2–17 years: in 4 (30.8 %) C1, in 4 (30.8 %) C2, in 3 (23 %) C3, in 1 (7.7 %) C4, in 1 (7.7 %) C5.