Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Paola Carrera, Silvia Calzavara, Riccardo Magistroni, Johan T. Den Dunnen, Francesca Rigo, Stefania Stenirri, Francesca Testa, Piergiorgio Messa, Roberta Cerutti, Francesco Scolari, Claudia Izzi, Alberto Edefonti, Susanna Negrisolo, Elisa Benetti, Maria Teresa Sciarrone Alibrandi, Paolo Manunta, Alessandra Boletta, Maurizio Ferrari

Research output: Contribution to journalArticlepeer-review

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary kidney disease. We analysed PKD1 and PKD2, in a large cohort of 440 unrelated Italian patients with ADPKD and 203 relatives by direct sequencing and MLPA. Molecular and detailed phenotypic data have been collected and submitted to the PKD1/PKD2 LOVD database. This is the first large retrospective study in Italian patients, describing 701 variants, 249 (35.5%) already associated with ADPKD and 452 (64.5%) novel. According to the criteria adopted, the overall detection rate was 80% (352/440). Novel variants with uncertain significance were found in 14% of patients. Among patients with pathogenic variants, in 301 (85.5%) the disease is associated with PKD1, 196 (55.7%) truncating, 81 (23%) non truncating, 24 (6.8%) IF indels, and in 51 (14.5%) with PKD2. Our results outline the high allelic heterogeneity of variants, complicated by the presence of variants of uncertain significance as well as of multiple variants in the same subject. Classification of novel variants may be particularly cumbersome having an important impact on the genetic counselling. Our study confirms the importance to improve the assessment of variant pathogenicity for ADPKD; to this point databasing of both clinical and molecular data is crucial.

Original languageEnglish
Article number30850
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Aug 8 2016

ASJC Scopus subject areas

  • General

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