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Genetica e scienze omiche/modelli sperimentali/trasduzione del segnale

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD): PKD1 AND PKD2 MUTATIONAL SCREENING IN ITALIAN PATIENTS

Questo Abstract è stato accettato come Poster.

Razionale

Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disorder (1:400/1000), is characterized by the development and progressive enlargement of renal cysts leading to ESKD. ADPKD is typically diagnosed by imaging methods, that may be uncertain especially in young individuals (<30 years) and in patients with a negative family history. ADPKD is caused by mutations in PKD1 or PKD2 genes.  Although, clinical studies and case reports describing one or few families have been reported in Italian population, to date a comprehensive molecular study of ADPKD is still lacking. 

Casistica e Metodi

PKD1 and PKD2 genes were analyzed in 100 ADPKD Italian patients - the largest Italian cohort analyzed to date in a single study - by direct sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA) and RNA analysis. The potential pathogenicity of the newly identified missense variants was evaluated by combining different methods: PolyPhen, SIFT and Mutation Taster.


Risultati

We identified the largest number of pathogenic mutations (n = 50) reported in a single study in Italian population. The mutations are of all different type (missense, nonsense, splice site, small deletions and insertions) and are spread over the exons of genes. Twenty PKD1 mutations have not been previously described and 10 were de novo, providing in such sporadic cases a definitive diagnosis of ADPKD. Three novel PKD1 mutations were found in ≥2 unrelated patients in our cohort. Notably, all of these recurrent mutations were found in patients from Southern Italy, a sign of founder mutations. 

Conclusioni

Our study represents a significant advance in the molecular diagnosis of ADPKD Italian patients because it (1) provides largest number of mutations reported in a single study in Italian population; (2) describes new potential founder mutations in patients from Southern Italy and 3) emphasizes the important role of mutational screening in ADPKD sporadic patients for the definitive diagnosis. 

M. Gigante, F. Bruno, S. Diella, B. Infante, E. Ranieri, G. Stallone, G. Grandaliano, L. Gesualdo
(Nephrology, Dialysis and Transplantation Unit, Dept. of Medical and Surgical Sciences, University of Foggia; Nephrology, Dialysis and Transplantation Unit, Dept. of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Italy )
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Realizzazione: Tesi S.p.A.

Per assistenza contattare: Lucia Piumetto, Tesi S.p.A.
0172 476301 — lucia.piumetto@gruppotesi.com