What are the most common kidney problems associated with HNF1B-MODY (RCAD syndrome)?

Individuals with HNF1B-MODY frequently develop kidney abnormalities, with the most common being renal cysts (fluid-filled sacs on the kidneys). Other kidney issues can include hypoplastic kidneys (underdeveloped kidneys), single kidney, abnormal kidney shape, or impaired kidney function, which can range from mild to severe and sometimes require dialysis or kidney transplant. These kidney problems are often present from birth.

HNF1B gene

The HNF1B gene provides instructions for a transcription factor essential for the development of several organs, including the kidneys and pancreas.

Normal Function

The HNF1B gene provides instructions for making a protein called hepatocyte nuclear factor-1 beta (HNF-1β). This protein acts as a transcription factor, attaching to specific regions of DNA to regulate the activity of other genes. It belongs to a group of transcription factors called homeodomain proteins.

The HNF-1β protein is found in many organs and tissues, including the lungs, liver, intestines, pancreas, kidneys, genital tract, and urinary tract. It is particularly important for the development and function of the kidneys and the beta cells in the pancreas. Beta cells produce and release insulin, which helps regulate blood sugar levels.

Health Conditions Related to Genetic Changes

Maturity-onset diabetes of the young

Mutations in the HNF1B gene cause a type of maturity-onset diabetes of the young (MODY) known as renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5). In addition to diabetes, affected individuals typically have kidney abnormalities, such as fluid-filled sacs called cysts. They may also experience abnormalities of the pancreas, liver, or genital tract, or a form of arthritis called gout.

17q12 deletion syndrome

17q12 deletion syndrome results from the deletion of a small piece of chromosome 17. This region contains at least 15 genes, including HNF1B. A loss of one copy of the HNF1B gene leads to a reduced amount of HNF-1β protein, which disrupts the regulation of genes necessary for the normal development of the kidneys and pancreas, often resulting in RCAD syndrome.

Congenital anomalies of kidney and urinary tract

Mutations within the HNF1B gene are found in people with congenital anomalies of kidney and urinary tract (CAKUT) without other features of RCAD or 17q12 deletion syndrome. These abnormalities vary in severity and can lead to kidney damage and life-threatening kidney failure.

Other Names for This Gene

FJHN
hepatocyte nuclear factor 1B
HNF-1-beta
HNF-1B
HNF1 beta A
HNF1beta
HNF2
homeoprotein LFB3
HPC11
LF-B3
LFB3
TCF-2
TCF2
transcription factor 2, hepatic
VHNF1

Genomic Location

The HNF1B gene is found on chromosome 17.