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 language | English |
|---|---|
| Article number | 30850 |
| Journal | Scientific Reports |
| Volume | 6 |
| DOIs | |
| Publication status | Published - Aug 8 2016 |
Fingerprint
ASJC Scopus subject areas
- General
Cite this
Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). / Carrera, Paola; Calzavara, Silvia; Magistroni, Riccardo; Den Dunnen, Johan T.; Rigo, Francesca; Stenirri, Stefania; Testa, Francesca; Messa, Piergiorgio; Cerutti, Roberta; Scolari, Francesco; Izzi, Claudia; Edefonti, Alberto; Negrisolo, Susanna; Benetti, Elisa; Alibrandi, Maria Teresa Sciarrone; Manunta, Paolo; Boletta, Alessandra; Ferrari, Maurizio.
In: Scientific Reports, Vol. 6, 30850, 08.08.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)
AU - Carrera, Paola
AU - Calzavara, Silvia
AU - Magistroni, Riccardo
AU - Den Dunnen, Johan T.
AU - Rigo, Francesca
AU - Stenirri, Stefania
AU - Testa, Francesca
AU - Messa, Piergiorgio
AU - Cerutti, Roberta
AU - Scolari, Francesco
AU - Izzi, Claudia
AU - Edefonti, Alberto
AU - Negrisolo, Susanna
AU - Benetti, Elisa
AU - Alibrandi, Maria Teresa Sciarrone
AU - Manunta, Paolo
AU - Boletta, Alessandra
AU - Ferrari, Maurizio
PY - 2016/8/8
Y1 - 2016/8/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84981165068&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84981165068&partnerID=8YFLogxK
U2 - 10.1038/srep30850
DO - 10.1038/srep30850
M3 - Article
AN - SCOPUS:84981165068
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 30850
ER -