Background: Maturity onset diabetes of young (MODY) type 5 is a form of non-insulin-dependent diabetes mellitus associated with renal cysts. It is an autosomal dominant disorder caused by mutations in the gene encoding hepatocyte nuclear factor-1beta (HNF-1beta). Methods: We performed molecular screening of HNF-1beta in a 13-year-old patient and his affected father, and analyzed polycystic kidney disease 2 (PKD2) gene and suppressor of cytokine signaling 3 (SOCS3) expression in lymphoblastoid cell lines and lymphocytes from both patients. Results: We found a novel HNF-1beta frameshift mutation (c.C1304del) that results in a truncated protein (p.I434IfsX1). The genetic change is localized in the transactivated protein domain. Conclusions: We demonstrated that this novel HNF-1beta mutation strongly influences the expression of both PKD2, responsible for the formation of the renal cysts, and SOCS3, which is associated with early diabetes onset.

HNF-1β mutation affects PKD2 and SOCS3 expression causing renal cysts and diabetes in MODY5 kindred.

BELLINI, Giulia;Roberti D;CASALE, Maddalena;ROSSI, Francesca;DELLA RAGIONE, Fulvio;PERROTTA, Silverio
2013

Abstract

Background: Maturity onset diabetes of young (MODY) type 5 is a form of non-insulin-dependent diabetes mellitus associated with renal cysts. It is an autosomal dominant disorder caused by mutations in the gene encoding hepatocyte nuclear factor-1beta (HNF-1beta). Methods: We performed molecular screening of HNF-1beta in a 13-year-old patient and his affected father, and analyzed polycystic kidney disease 2 (PKD2) gene and suppressor of cytokine signaling 3 (SOCS3) expression in lymphoblastoid cell lines and lymphocytes from both patients. Results: We found a novel HNF-1beta frameshift mutation (c.C1304del) that results in a truncated protein (p.I434IfsX1). The genetic change is localized in the transactivated protein domain. Conclusions: We demonstrated that this novel HNF-1beta mutation strongly influences the expression of both PKD2, responsible for the formation of the renal cysts, and SOCS3, which is associated with early diabetes onset.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/185546
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