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


METHODS
We performed molecular screening of HNF-1β 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-1β 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-1β 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.
Department of Pediatrics, Second University of Naples, Italy.
Silvia
S
Mancusi
Angela
A
La Manna
Giulia
G
Bellini
Saverio
S
Scianguetta
Domenico
D
Roberti
Maddalena
M
Casale
Francesca
F
Rossi
Fulvio
F
Della Ragione
Silverio
S
Perrotta
D000293:Adolescent; D016022:Case-Control Studies; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003743:Dental Enamel / Q000002:abnormalities / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D016368:Frameshift Mutation; D015870:Gene Expression; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes; D008297:Male; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D050396:TRPP Cation Channels / Q000235:genetics*
D051539:Hepatocyte Nuclear Factor 1-beta; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D050396:TRPP Cation Channels; C496495:HNF1B protein, human; C106644:SOCS3 protein, human