Autosomal dominant polycystic kidney disease (ADPKD) in Tunisia: From molecular genetics to the development of prognostic tools

Abstract

A high prevalence of genetic kidney disease in Tunisia has been detected, and their study provides very important clinical and genetic information. Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of morbidity and mortality associated with the kidneys in Tunisia. We present here clinical and genetic characteristics of a cohort of Tunisian patients with ADPKD. Nineteen Tunisian patients with ADPKD, among 4 familial cases and 11 sporadic cases, and 50 Healthy individuals were included in this cohort. Genetic studies of PKD1/2 were carried on using Sanger sequencing and MLPA. In our study, the mean age at diagnosis was 47 ± 18 years. In addition, 84.21% of cases present a family history of ADPKD. Overall, 57.89% of the affected individuals had HTA and 26.31% patients had hematuria. 15.78 % of the patient has extra-renal cysts i.e. one patient with splenic cysts and two patients had liver cysts. 57.89 % of patients were diagnosed with various extra-renal clinical presentations i.e. myopia, hernia, deafness, intracranial aneurysm, respiratory distress, hyperthyroidism, urinary tract infection and lower back pains. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (43 vs. 55 years old). Six mutations have been detected in PKD1 gene. Among them, three were novels e.g. c.688 T>G, p.C230G and c.690C>G, p.C230W among exon 5 and c.8522A>G, p.N2841S among exon 23. In addition, thirteen single nucleotides polymorphisms have been reported in PKD1 gene. Among them, eleven previously reported in heterozygous state and two novel single nucleotides polymorphisms in heterozygous and homozygous state and predicted to be probable polymorphisms by computational tools: c.496C>T, p.L166= among the exon 4, and c.10165G>C and p.E3389Gln among the exon 31. Only three single nucleotides polymorphisms previously reported in ADPKD database have been identified in PKD2 gene. The description and analysis of our cohort can help in rapid and reliable diagnosis for early management of patients in Tunisia. Indeed, predictive genetic testing can facilitate donor evaluation and increase living related kidney transplantation.

Keywords: Functional effect; Mutation; PKD1 gene; PKD2 gene; Single nucleotide polymorphism.