Renal Malformations May Be Linked to Mutations in the Hepatocyte Nuclear Factor-1α (MODY3) Gene
- Maciej T. Malecki, MD, PHD1,
- Jan Skupien, MD1,
- Sylwia Gorczynska-Kosiorz, PHD2,
- Tomasz Klupa, MD, PHD1,
- Joanna Nazim, MD, PHD3,
- Dariusz K. Moczulski, MD, PHD2 and
- Jacek Sieradzki, MD, PHD1
- 1Department of Metabolic Diseases, Jagiellonian University, Medical College, Krakow, Poland
- 2Department of Internal Medicine, Diabetology, and Nephrology, Silesian School of Medicine, Zabrze, Poland
- 3Department of Paediatric Endocrinology, Polish-American Children’s Hospital, Jagiellonian University, Medical College, Krakow, Poland
- Address correspondence and reprint requests to Maciej T. Malecki, Department of Metabolic Diseases, Jagiellonian University, Medical College, 15 Kopernika St., 31-501 Krakow, Poland. E-mail: malecki_malecki{at}yahoo.com or mmalecki{at}cm-uj.krakow.pl
Maturity-onset diabetes of the young (MODY) is an autosomal- dominant form of disease characterized by β-cell defects and early age of diagnosis. So far, six MODY genes have been identified (1,2). MODY is sometimes accompanied by extrapancreatic features such as developmental malformations and physiological and biochemical abnormalities (3). The most frequent MODY3 subtype is caused by mutations in the hepatocyte nuclear factor (HNF)-1α gene, a transcription factor expressed in pancreas, kidney, liver, and gut.
RESEARCH DESIGN AND METHODS
To dissect the genetic background and to provide clinical characteristics of this form of diabetes in Poland, the Nationwide Registry was established in 2004 at the Department of Metabolic Diseases, Jagiellonian University Medical College in Krakow. So far, 30 families with the early-onset, autosomal- dominant form of diabetes meeting commonly used criteria of MODY (diabetes occurring in at least three generations and at least two individuals diagnosed with diabetes before the age of 25 years) were included in this program. The subjects from those families received a standard questionnaire that contained questions regarding the age of diabetes diagnosis, family history, treatment method, and other medical issues. Fasting blood was drawn for plasma glucose determinations, other biochemical measurements, and DNA extraction. The study protocol and informed consent procedures were approved by the ethical committee of the Jagiellonian University, Medical College. The project is conducted according to the rules of the Helsinki Declaration.
RESULTS
In the process of screening for HNF-1α (MODY3) mutations, the 10 exons and promoter region of the gene were analyzed by direct sequencing of the PCR …
